A group of homologous proteins which form the intermembrane channels of GAP JUNCTIONS. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions.
Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of CONNEXINS, the family of proteins which form the junctions.
A 43-kDa peptide which is a member of the connexin family of gap junction proteins. Connexin 43 is a product of a gene in the alpha class of connexin genes (the alpha-1 gene). It was first isolated from mammalian heart, but is widespread in the body including the brain.
Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
A transparent, biconvex structure of the EYE, enclosed in a capsule and situated behind the IRIS and in front of the vitreous humor (VITREOUS BODY). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the CILIARY BODY is crucial for OCULAR ACCOMMODATION.
Direct contact of a cell with a neighboring cell. Most such junctions are too small to be resolved by light microscopy, but they can be visualized by conventional or freeze-fracture electron microscopy, both of which show that the interacting CELL MEMBRANE and often the underlying CYTOPLASM and the intervening EXTRACELLULAR SPACE are highly specialized in these regions. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p792)
An agent derived from licorice root. It is used for the treatment of digestive tract ulcers, especially in the stomach. Antidiuretic side effects are frequent, but otherwise the drug is low in toxicity.
Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
The study of the origin, structure, development, growth, function, genetics, and reproduction of plants.
Preparation for electron microscopy of minute replicas of exposed surfaces of the cell which have been ruptured in the frozen state. The specimen is frozen, then cleaved under high vacuum at the same temperature. The exposed surface is shadowed with carbon and platinum and coated with carbon to obtain a carbon replica.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
An oleanolic acid from GLYCYRRHIZA that has some antiallergic, antibacterial, and antiviral properties. It is used topically for allergic or infectious skin inflammation and orally for its aldosterone effects in electrolyte regulation.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.
A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
A 195-kDa zonula occludens protein that is distinguished by the presence of a ZU5 domain at the C-terminal of the molecule.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
A plant genus of the family RUBIACEAE. Members contain antimalarial (ANTIMALARIALS) and analgesic (ANALGESICS) indole alkaloids.
A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
A colorless liquid with a fragrant odor. It is used as an intermediate, solvent and in cosmetics.
Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.
The portion of an interactive computer program that issues messages to and receives commands from a user.
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
Sequential operating programs and data which instruct the functioning of a digital computer.
NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A CX3C chemokine that is a transmembrane protein found on the surface of cells. The soluble form of chemokine CX3CL1 can be released from cell surface by proteolysis and act as a chemoattractant that may be involved in the extravasation of leukocytes into inflamed tissues. The membrane form of the protein may also play a role in cell adhesion.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
A nonreducing disaccharide composed of GLUCOSE and FRUCTOSE linked via their anomeric carbons. It is obtained commercially from SUGARCANE, sugar beet (BETA VULGARIS), and other plants and used extensively as a food and a sweetener.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
Immunoglobulins produced in response to VIRAL ANTIGENS.
Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy.
Antibodies produced by a single clone of cells.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Lectins purified from the germinating seeds of common wheat (Triticum vulgare); these bind to certain carbohydrate moieties on cell surface glycoproteins and are used to identify certain cell populations and inhibit or promote some immunological or physiological activities. There are at least two isoforms of this lectin.
Proteins prepared by recombinant DNA technology.
A plant genus of the family POACEAE that is the source of EDIBLE GRAIN. A hybrid with rye (SECALE CEREALE) is called TRITICALE. The seed is ground into FLOUR and used to make BREAD, and is the source of WHEAT GERM AGGLUTININS.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Formation of NEURONS which involves the differentiation and division of STEM CELLS in which one or both of the daughter cells become neurons.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

Gap junction signalling mediated through connexin-43 is required for chick limb development. (1/2276)

During chick limb development the gap junction protein Connexin-43 (Cx43) is expressed in discrete spatially restricted domains in the apical ectodermal ridge (AER) and mesenchyme of the zone of polarising activity. Antisense oligonucleotides (ODNs) were used to investigate the role of Connexin-43 (Cx43) in the development of the chick limb bud. We have used unmodified ODNs in Pluronic F-127 gel, which is liquid at low temperature but sets at room temperature and so remains situated at the point of application. As a mild surfactant, the gel increases antisense ODN penetration and supplies ODNs to the embryo continually for 12-18 h. We have shown a strong decrease in Cx43 protein expression after application of specific antisense oligonucleotides but the abundance of a closely related protein, Connexin-32 (Cx32), was not affected. Application of antisense Cx43 ODNs at stages 8-15 HH before limb outgrowth resulted in dramatic limb phenotypes. About 40% of treated embryos exhibited defects such as truncation of the limb bud, fragmentation into two or more domains, or complete splitting of the limb bud into two or three branches. Molecular analysis of antisense treated embryos failed to detect Shh or Bmp-2 in anterior structures and suggested that extra lobes seen in nicked and split limbs were not a result of establishment of new signalling centres as found after the application of FGF to the flank. However, examination of markers for the AER showed a number of abnormalities. In severely truncated specimens we were unable to detect the expression of either Fgf-4 or Fgf-8. In both nicked and split limbs the expression of these genes was discontinuous. Down-regulation of Cx43 after the antisense application could be comparable to AER removal and results in distal truncation of the limb bud. Taken together these data suggest the existence of a feedback loop between the FGFs and signalling mediated by Cx43.  (+info)

Chemical signaling from colonic smooth muscle cells to DRG neurons in culture. (2/2276)

Transduction mechanisms between target cells within the intestinal wall and peripheral terminals of extrinsic primary afferent neurons are poorly understood. The purpose of this study was to characterize the interactions between smooth muscle cells from the rat distal colon and lumbar dorsal root ganglion (DRG) neurons in coculture. DRG neurons visually appeared to make contact with several myocytes. We show that brief mechanical stimulation of these myocytes resulted in intracellular Ca2+ concentration ([Ca2+]i) transients that propagated into 57% of the contacting neurites. Direct mechanical stimulation of DRG neurites cultured without smooth muscle had no effect. We also show that colonic smooth muscle cells express multiple connexin mRNAs and that these connexins formed functional gap junctions, as evidenced by the intercellular transfer of Lucifer yellow. Furthermore, thapsigargin pretreatment and neuronal heparin injection abolished the increase in neurite [Ca2+]i, indicating that the neuronal Ca2+ signal was triggered by inositol 1,4, 5-trisphosphate-mediated Ca2+ release from intracellular stores. Our results provide evidence for intercellular chemical communication between DRG neurites and intestinal smooth muscle cells that mediates the exchange of second messenger molecules between different cell types.  (+info)

Central visual, acoustic, and motor pathway involvement in a Charcot-Marie-Tooth family with an Asn205Ser mutation in the connexin 32 gene. (3/2276)

BACKGROUND: X linked dominant Charcot-Marie-Tooth disease (CMT1X) is an inherited motor and sensory neuropathy that mainly affects the peripheral nervous system. CMT1X is associated with mutations in the gap junction protein connexin 32 (Cx32). Cx32 is expressed in Schwann cells and oligodendrocytes in the peripheral (PNS) and in the (CNS) respectively. METHODS: A CMT1X family with a Cx32 mutation was examined clinically and electrophysiologically to determine whether PNS, or CNS, or both pathways were affected. RESULTS: In a CMT1X family a novel mutation (Asn205Ser) was found in the fourth transmembrane domain of Cx32. The patients showed typical clinical and electrophysiological abnormalities in the PNS, but in addition visual, acoustic, and motor pathways of the CNS were affected subclinically. This was indicated by pathological changes in visually evoked potentials (VEPs), brainstem auditory evoked potentials (BAEPs), and central motor evoked potentials (CMEPs). CONCLUSIONS: These findings underscore the necessity of a careful analysis of CNS pathways in patients with CMT and Cx32 mutations. Abnormal electrophysiological findings in CNS pathway examinations should raise the suspicion of CMTX and a search for gene mutations towards Cx32 should be considered.  (+info)

Upregulation of connexin 26 is a feature of keratinocyte differentiation in hyperproliferative epidermis, vaginal epithelium, and buccal epithelium. (4/2276)

In epidermis, it has been suggested, intercellular communication through gap junctions is important in coordinating cell behavior. The connexins, may facilitate selective assembly or permeability of gap junctions, influencing the distribution of metabolites between cells. Using immunohistochemistry, we have compared the distribution of connexins 26 and 43 with that of proliferating cells (Ki67 labeling) in normal epidermis, hyperplastic epidermis (tape-stripped epidermis, psoriatic lesions, and viral warts), and vaginal and buccal epithelia. Connexin 43 was abundant in spinous layers of all epidermal specimens and in vaginal and buccal epithelia. Connexin 26 was absent from the interfollicular and interductal epidermis of normal hair-bearing skin, and nonlesional psoriatic epidermis but present at very low levels in plantar epidermis. Connexin 26 was prominent in lesional psoriatic epidermis and viral warts and in vaginal and buccal epithelia. In three independent experiments connexin 26 appeared in a patchy intercellular distribution in the basal epidermis within 24 h of tape stripping, proceeding to more extensive distribution in basal and suprabasal layers by 48 h. The increase in connexin 26 preceded that in cell proliferation. In vaginal epithelium, buccal epithelium, and viral warts connexin 26 was restricted mainly to suprabasal, nonproliferating cells. In psoriatic lesional epidermis connexin 26 was also located mainly in suprabasal, nonproliferating cells. Connexin 26 was present in a patchy distribution in the basal layer of psoriatic lesional epidermis, but double labeling for connexin 26 and Ki67 showed that many connexin 26 positive basal cells were nonproliferative, suggesting that connexin 26 may be related to differentiation rather than to proliferation. These observations would be consistent with a role for connexin 26 containing gap junctions during both early and later stages of keratinocyte differentiation in hyperplastic epidermis and in vaginal and buccal epithelia.  (+info)

Intracellular trafficking pathways in the assembly of connexins into gap junctions. (5/2276)

Trafficking pathways underlying the assembly of connexins into gap junctions were examined using living COS-7 cells expressing a range of connexin-aequorin (Cx-Aeq) chimeras. By measuring the chemiluminescence of the aequorin fusion partner, the translocation of oligomerized connexins from intracellular stores to the plasma membrane was shown to occur at different rates that depended on the connexin isoform. Treatment of COS-7 cells expressing Cx32-Aeq and Cx43-Aeq with brefeldin A inhibited the movement of these chimera to the plasma membrane by 84 +/- 4 and 88 +/- 4%, respectively. Nocodazole treatment of the cells expressing Cx32-Aeq and Cx43-Aeq produced 29 +/- 16 and 4 +/- 7% inhibition, respectively. In contrast, the transport of Cx26 to the plasma membrane, studied using a construct (Cx26/43T-Aeq) in which the short cytoplasmic carboxyl-terminal tail of Cx26 was replaced with the extended carboxyl terminus of Cx43, was inhibited 89 +/- 5% by nocodazole and was minimally affected by exposure of cells to brefeldin A (17 +/-11%). The transfer of Lucifer yellow across gap junctions between cells expressing wild-type Cx32, Cx43, and the corresponding Cx32-Aeq and Cx43-Aeq chimeras was reduced by nocodazole treatment and abolished by brefeldin A treatment. However, the extent of dye coupling between cells expressing wild-type Cx26 or the Cx26/43T-Aeq chimeras was not significantly affected by brefeldin A treatment, but after nocodazole treatment, transfer of dye to neighboring cells was greatly reduced. These contrasting effects of brefeldin A and nocodazole on the trafficking properties and intercellular dye transfer are interpreted to suggest that two pathways contribute to the routing of connexins to the gap junction.  (+info)

Conduction disturbances and increased atrial vulnerability in Connexin40-deficient mice analyzed by transesophageal stimulation. (6/2276)

BACKGROUND: Recently, it has been reported that connexin40 (Cx40) deficiency in targeted mouse mutants is associated with a prolongation of P-wave and QRS complex duration on surface electrograms. The specific effects of Cx40 deficiency on sinus node function, sinoatrial, and atrioventricular conduction properties as well as on atrial vulnerability have not yet been investigated systematically by electrophysiological analysis. METHODS AND RESULTS: Fifty-two mice (18 Cx40(+/+), 15 Cx40(+/-), and 19 Cx40(-/-) mice) were subjected to rapid atrial transesophageal stimulation after anesthesia with avertin. A significant prolongation of sinus node recovery time was noticed in Cx40(-/-) mice compared with Cx40(+/-) and Cx40(+/+) mice (287.8+/-109.0 vs 211.1+/-61.8 vs 204.4+/-60.9 ms; P<0.05). In addition, Wenckebach periodicity occurred at significantly longer atrial pacing cycle lengths in Cx40(-/-) mice than in Cx40(+/-) or Cx40(+/+) mice (93. 3+/-11.8 vs 83.9+/-9.7 vs 82.8+/-8.0 ms, P<0.05). Analysis of 27 Cx40(-/-) mice showed a significant increase in intra-atrial conduction time and atrioventricular conduction time compared with 52 Cx40(+/-) and 31 wild-type (Cx40(+/+)) mice. Furthermore, in Cx40(-/-) mice, atrial tachyarrhythmias could be induced frequently by atrial burst pacing, whereas no atrial arrhythmias were inducible in heterozygous or wild-type mice. CONCLUSIONS: This study demonstrates that Cx40 deficiency is associated with sinoatrial, intra-atrial, and atrioventricular conduction disturbances. In atrial myocardium of the mouse, Cx40 deficiency results in increased atrial vulnerability and might contribute to arrhythmogenesis.  (+info)

Are human placental bed giant cells merely aggregates of small mononuclear trophoblast cells? An ultrastructural and immunocytochemical study. (7/2276)

The ultrastructure of placental bed giant cells in early human pregnancies of 7-12 weeks gestational age is described. Their nature and function was further characterized by confocal immunofluorescence microscopy of paraffin sections labelled for cytokeratin, gap junction connexins (CX) 32 or 43, and placental hormones, alpha-human chorionic gonadotrophin (alpha-HCG) and human placental lactogen (HPL). Placental bed giant cells were observed with two phenotypes; as single large trophoblast cells containing one or more nuclear profiles in a voluminous cytoplasm, and as cell aggregates comprising mononuclear trophoblast cells in close apposition separated by narrow intercellular spaces. Cells within the aggregates are attached to one another by desmosomes, and also possess gap junctions as shown by immunolabelling for CX32 and CX43. By contrast, gap junctions were absent in the true multinucleated giant cells. Organelles present within the cytoplasm of the giant cells and their immunoreactivity for HPL and alpha-HCG suggest protein synthesis.  (+info)

Functional and morphological correlates of connexin50 expressed in Xenopus laevis oocytes. (8/2276)

Electrophysiological and morphological methods were used to study connexin50 (Cx50) expressed in Xenopus laevis oocytes. Oocytes expressing Cx50 exhibited a new population of intramembrane particles (9.0 nm in diameter) in the plasma membrane. The particles represented hemichannels (connexin hexamers) because (a) their cross-sectional area could accommodate 24 +/- 3 helices, (b) when their density reached 300-400/microm2, they formed complete channels (dodecamers) in single oocytes, and assembled into plaques, and (c) their appearance in the plasma membrane was associated with a whole-cell current, which was activated at low external Ca2+ concentration ([Ca2+]o), and was blocked by octanol and by intracellular acidification. The Cx50 hemichannel density was directly proportional to the magnitude of the Cx50 Ca2+-sensitive current. Measurements of hemichannel density and the Ca2+-sensitive current in the same oocytes suggested that at physiological [Ca2+]o (1-2 mM), hemichannels rarely open. In the cytoplasm, hemichannels were present in approximately 0.1-microm diameter "coated" and in larger 0.2-0.5-microm diameter vesicles. The smaller coated vesicles contained endogenous plasma membrane proteins of the oocyte intermingled with 5-40 Cx50 hemichannels, and were observed to fuse with the plasma membrane. The larger vesicles, which contained Cx50 hemichannels, gap junction channels, and endogenous membrane proteins, originated from invaginations of the plasma membrane, as their lumen was labeled with the extracellular marker peroxidase. The insertion rate of hemichannels into the plasma membrane (80, 000/s), suggested that an average of 4,000 small coated vesicles were inserted every second. However, insertion of hemichannels occurred at a constant plasma membrane area, indicating that insertion by vesicle exocytosis (60-500 microm2 membranes/s) was balanced by plasma membrane endocytosis. These exocytotic and endocytotic rates suggest that the entire plasma membrane of the oocyte is replaced in approximately 24 h.  (+info)

Our experiments indicate that the incidence of electrical coupling in parental HeLa cells and RIN cells is low. After transfection with Cx40 or Cx43, coupling was enhanced ≈200-fold in Cx40-HeLa-Cx43-HeLa and Cx40-HeLa-Cx43-RIN cell pairs. This suggests formation of heterotypic Cx40-Cx43 channels.. The multichannel and single-channel data presented indicate that Cx40-Cx43 channels are present in Cx40-HeLa-Cx43-HeLa and Cx40-HeLa-Cx43-RIN cell pairs. With regard to multichannel data, the relationships gj, inst=f(Vj) and gj, ss=f(Vj) were asymmetrical, a property seen in heterotypic gap junctions whose connexons exhibit widely different properties (eg, Cx26-Cx3216 17 18 or Cx37-Cx43.12 21 In the case of Cx40-Cx43, rectification was prominent for both relationships, ie, gj, ss=f(Vj) and gj, inst=f(Vj) (see Figures 2C⇑ and 2D⇑). Voltage gating was almost exclusively observed at negative Vj. This is consistent with the notion that Cx40 is gating with positive polarity (V.V., R.W., P.R.B., ...
TY - JOUR. T1 - Molecular cloning and functional expression of mouse connexin-30, a gap junction gene highly expressed in adult brain and skin. AU - Dahl, Edgar. AU - Manthey, Dieter. AU - Chen-Izu, Ye. AU - Schwarz, Hans Jürgen. AU - Chang, Young Sook. AU - Lalley, Peter A.. AU - Nicholson, Bruce J.. AU - Willecke, Klaus. PY - 1996. Y1 - 1996. N2 - A new gap junction gene isolated from the mouse genome codes for a connexin protein of 261 amino acids. Because of its theoretical molecular mass of 30.366 kDa, it is named connexin-30. Within the connexin gene family, this protein is most closely related to connexin-26 (77% amino acid sequence identity). The coding region of mouse connexin-30 is uninterrupted by introns and is detected in the mouse genome as a single copy gene that is assigned to mouse chromosome 14 by analysis of mouse x hamster somatic cell hybrids. Abundant amounts of connexin-30 mRNA (two transcripts of 2.0 and 2.3 kilobase pairs) were found after 4 weeks of postnatal ...
TY - JOUR. T1 - The molecular basis of selective permeability of connexins is complex and includes both size and charge. AU - Nicholson, B. J.. AU - Weber, P. A.. AU - Cao, F.. AU - Chang, H. C.. AU - Lampe, P.. AU - Goldberg, G.. PY - 2000/4. Y1 - 2000/4. N2 - Although gap junction channels are still widely viewed as large, non-specific pores connecting cells, the diversity in the connexin family has led more attention to be focused on their permeability characteristics. We summarize here the current status of these investigations, both published and on-going, that reveal both charge and size selectivity between gap junction channels composed of different connexins. In particular, this review will focus on quantitative approaches that monitor the expression level of the connexins, so that it is clear that differences that are seen can be attributed to channel properties. The degree of selectivity that is observed is modest compared to other channels, but is likely to be significant for ...
TY - JOUR. T1 - Correlations of differentially expressed gap junction connexins cx26, cx30, cx32, cx43 and cx46 with breast cancer progression and prognosis. AU - Teleki, Ivett. AU - Szász, A.. AU - Maros, Mate Elod. AU - Györffy, B.. AU - Kulka, J.. AU - Meggyeshazi, Nora. AU - Kiszner, Gergo. AU - Balla, Peter. AU - Samu, Aliz. AU - Krenács, T.. PY - 2014/11/10. Y1 - 2014/11/10. N2 - Background and Aims: Connexins and their cell membrane channels contribute to the control of cell proliferation and compartmental functions in breast glands and their deregulation is linked to breast carcinogenesis. Our aim was to correlate connexin expression with tumor progression and prognosis in primary breast cancers.Materials and Methods: Meta-analysis of connexin isotype expression data of 1809 and 1899 breast cancers from the Affymetrix and Illumina array platforms, respectively, was performed. Expressed connexins were also monitored at the protein level in tissue microarrays of 127 patients equally ...
Connexin 30 (Cx30), a member of the large gap junction protein family, plays a role in the homeostasis of the epidermis and inner ear through gap junctional intercellular communication (GJIC). Here, we investigated the underlying mechanisms of four autosomal dominant Cx30 gene mutations linked to hearing loss and/or various skin diseases. First, the T5M mutant linked to non-syndromic hearing loss formed functional gap junction channels and hemichannels, similar to wild type Cx30. The loss-of-function V37E mutant associated with Clouston syndrome or keratitis-ichthyosis-deafness syndrome was retained in the endoplasmic reticulum and significantly induced apoptosis. The G59R mutant linked to Vohwinkel and Bart-Pumphrey syndromes was retained primarily in the Golgi apparatus and exhibited loss of gap junction channel and hemichannel function, but did not cause cell death. Lastly, the A88V mutant related to Clouston syndrome also significantly induced apoptosis, although through an endoplasmic ...
TY - JOUR. T1 - Regulation of connexin hemichannels by monovalent cations. AU - Srinivas, Miduturu. AU - Calderon, D. Paola. AU - Kronengold, Jack. AU - Verselis, Vytautas. PY - 2006/1. Y1 - 2006/1. N2 - Opening of connexin hemichannels in the plasma membrane is highly regulated. Generally, depolarization and reduced extracellular Ca2+ promote hemichannel opening. Here we show that hemichannels formed of Cx50, a principal lens connexin, exhibit a novel form of regulation characterized by extraordinary sensitivity to extracellular monovalent cations. Replacement of extracellular Na+ with K+, while maintaining extracellular Ca2+ constant, resulted in ,10-fold potentiation of Cx50 hemichannel currents, which reversed upon returning to Na+. External Cs+, Rb+, NH4+, but not Li +, choline, or TEA, exhibited a similar effect. The magnitude of potentiation of Cx50 hemichannel currents depended on the concentration of extracellular Ca2+, progressively decreasing as external Ca 2+ was reduced. The primary ...
Efficient inter-myocyte communication is essential for synchronised myocardial contraction. Gap junctions are areas where adjacent cell membranes are more closely apposed to each other. Within these gap junctions are present communication ports called connexins. Connexin channels are composed of two grummet shaped hemi-channels called connexons. Each connexon in turn is a hexamer of 6 connexin protein molecules. Connexin channels are selectively permeable to certain ions and molecules less than 1kDa in weight and less than 2nm in diameter. There are three isotypes of connexins expressed by the human myocardium, connexin-40 (Cx40), connexin-43 (Cx43), and connexin-45 (Cx45). Each isotype has distinct unitary conductance, permeability, and gating properties. Cx40 are high conductance channels expressed by atrial myocytes and the conduction system. Cx43 is mainly expressed by ventricular and to a lesser extent by atrial myocytes. Cx45 are low conductance channels mainly expressed by myocytes in the ...
Connexins (Cxs) and pannexins (Panxs) are highly regulated large-pore channel-forming proteins that participate in cellular communication via small molecular exchange with the extracellular microenvironment, or in the case of connexins, directly between cells. in Cx40?/? mice was further exaggerated in double knockout mice. Thus, while gestation and gross development were conserved in Cx40?/?Panx1?/? mice, they exhibit cardiac hypertrophy, hypertension, and impaired endothelial-mediated vasodilation that phenocopies Cx40?/? mice. Nevertheless, the augmented renin homeostasis observed in the double knockout mice suggests that both Cx40 and Panx1 may play an integrative role. [3C5]. Conversely, the most well-understood pannexin, pannexin1 (Panx1), has been demonstrated to form large-pore membrane channels, which facilitate autocrine/paracrine-mediated signaling via the release of purine nucleotides, most notably ATP [6]. Within the mammalian cardiovascular system (cardiac tissue and peripheral ...
Individual cell-cell channels consist of two hemichannels, located on neighboring cell membranes, that are interconnected to form an hydrophilic pathway. Each hemichannel, or connexon, is made of six protein subunits, called connexins.Connexin32 liver gap junction protein has four transmembrane segments, two extracellular regions and three cytoplasmic segments, which include the amino and carboxyl termini.The process of cell-cell channel formation was investigated by altering specific amino acids in the presumed extracellular domains of the connexin32. It is these domains that must interact when two hemichannels dock to form an open cell-cell channel. The mutant connexins were generated by site-directed in vitro mutagenesis of a connexin32 cDNA. The mutated cDNAs were then transcribed in vitro and the mRNA was injected into Xenopus oocytes for expression. Junctional conductances between paired oocytes resulting from the expression of the mRNA were measured by the double-voltage clamp technique.Every
Communication among cells via direct cell-cell contact by connexin gap junctions, or between cell and extracellular environment via pannexin channels or connexin hemichannels, is a key factor in cell...
Connexins (Cx) (TC# 1.A.24), or gap junction proteins, are structurally related transmembrane proteins that assemble to form vertebrate gap junctions. An entirely different family of proteins, the innexins, form gap junctions in invertebrates. Each gap junction is composed of two hemichannels, or connexons, which consist of homo- or heterohexameric arrays of connexins, and the connexon in one plasma membrane docks end-to-end with a connexon in the membrane of a closely opposed cell. The hemichannel is made of six connexin subunits which are themselves each constructed out of six connexin molecules[clarification needed]. Gap junctions are essential for many physiological processes, such as the coordinated depolarization of cardiac muscle, proper embryonic development, and the conducted response in microvasculature. For this reason, mutations in connexin-encoding genes can lead to functional and developmental abnormalities. Connexins are commonly named according to their molecular weights, e.g. ...
Gap junctions are intercellular channels made of connexins (Cxs) that allow direct communication between adjacent cells. Modulation of Cxs has been associated with abnormal development and function of the mammary gland and breast cancer. However, the mechanisms underlying their expression during normal mammary gland are not yet known. Cxs interact with components of tight and adherens junctions. Thus, we hypothesized that the expression levels of Cxs vary during mammary gland development and are regulated through stage-dependent interactions with members of the tight and adherens junctions. Our specific objectives were to: 1) determine the expression of Cxs and tight and adherens junction proteins throughout development and 2) characterize Cxs interactions with components of tight and adherens junctions. Murine mammary glands were sampled at various developmental stages (pre-pubescent to post-weaning). RT-qPCR and western-blot analyses demonstrated differential expression patterns for all gap ...
Abstract: Heart development is a precisely harmonized process of cellular proliferation, migration, differentiation, and integrated morphogenetic interactions, and therefore it is extremely vulnerable to developmental defects that cause congenital heart diseases (CHD). One of the major causes of CHD has been shown to be the mutations in key cardiac channel-forming proteins namely, connexins (Cxs). Cxs are tetra-spanning transmembrane proteins that form gap junction channels and hemichannels on cellular membrane. They allow passage of small molecules or ions between adjacent cells or between cells and the extracellular environment. Studies have revealed that the spatiotemporal expression of Cxs mainly, Cx31.9, Cx40, Cx43, and Cx45 is essentially involved in early developmental events, morphogenetic transformations, maturation, and functional significance of heart. Our lab and others have shown that mutations in gap junction proteins could result in impaired trafficking, misfolding, and improper ...
Pannexin2 (Panx2) is the largest of three members of the pannexin proteins. Pannexins are topologically related to connexins and innexins, but serve different functional roles than forming gap junctions. We previously showed that pannexins form oligomeric channels but unlike connexins and innexins, they form only single membrane channels. High levels of Panx2 mRNA and protein in the Central Nervous System (CNS) have been documented. Whereas Pannexin1 (Panx1) is fairly ubiquitous and Pannexin3 (Panx3) is found in skin and connective tissue, both are fully glycosylated, traffic to the plasma membrane and have functions correlated with extracellular ATP release. Here, we describe trafficking and subcellular localizations of exogenous Panx2 and Panx1 protein expression in MDCK, HeLa, and HEK 293T cells as well as endogenous Panx1 and Panx2 patterns in the CNS. Panx2 was found in intracellular localizations, was partially N-glycosylated, and localizations were non-overlapping with Panx1. Confocal images of
Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function, and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability, and function. Here, we summarize these key regulatory events, with emphasis on how these affect connexin multifunctionality in health and disease ...
1) Gap junction hyper-neurons. Stuart: Regarding my suggestion that gap junction-connected neurons (hyper-neurons) may be the neural correlate of consciousness, Christof raises the issue of connexin-36 (a brain gap junction protein) knockout mice who appear relatively normal from a cognitive standpoint, and are presumably conscious. (This exact point was debated on PSYCHE-B a year or so ago, raised by Johnjoe MacFadden). Christof notes that gamma synchrony continued in the knockout mice, though reduced.. As Christof notes, there at least ten types of connexins. Additional connexins are being discovered all the time. Further, another family of gap junction proteins - the pannexins - has been uncovered. So when Christof says: The most important connexin of the adult brain is Cx36, this is not necessarily the case. And to say that connexin-36 knockout mice lack functional gap junctions in their brains is an extremely weak contention (e.g. shown by the occurrence of even weak gamma synchrony). ...
1) Gap junction hyper-neurons. Stuart: Regarding my suggestion that gap junction-connected neurons (hyper-neurons) may be the neural correlate of consciousness, Christof raises the issue of connexin-36 (a brain gap junction protein) knockout mice who appear relatively normal from a cognitive standpoint, and are presumably conscious. (This exact point was debated on PSYCHE-B a year or so ago, raised by Johnjoe MacFadden). Christof notes that gamma synchrony continued in the knockout mice, though reduced.. As Christof notes, there at least ten types of connexins. Additional connexins are being discovered all the time. Further, another family of gap junction proteins - the pannexins - has been uncovered. So when Christof says: The most important connexin of the adult brain is Cx36, this is not necessarily the case. And to say that connexin-36 knockout mice lack functional gap junctions in their brains is an extremely weak contention (e.g. shown by the occurrence of even weak gamma synchrony). ...
Sigma-Aldrich offers abstracts and full-text articles by [Peter J Minogue, Jun-Jie Tong, Anita Arora, Isabelle Russell-Eggitt, David M Hunt, Anthony T Moore, Lisa Ebihara, Eric C Beyer, Viviana M Berthoud].
The three major blood cell types, i.e., platelets, erythrocytes and leukocytes, are all produced in the bone marrow. While red blood cells are the most numerous and white cells are the largest, platelets are small fragments and account for a minor part of blood volume. However, platelets display a crucial function by preventing bleeding. Upon vessel wall injury, platelets adhere to exposed extracellular matrix, become activated, and form a platelet plug preventing hemorrhagic events. However, when platelet activation is exacerbated, as in rupture of an atherosclerotic plaque, the same mechanism may lead to acute thrombosis causing major ischemic events such as myocardial infarction or stroke. In the past few years, major progress has been made in understanding of platelet function modulation. In this respect, membrane channels formed by connexins and/or pannexins are of particular interest. While it is still not completely understood whether connexins function as hemichannels or gap junction channels to
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This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Mutations in this gene may be associated with atrial fibrillation. Alternatively spliced transcript variants encoding the same isoform have been described. [provided by RefSeq, Jul 2008 ...
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Connexins (Cxs) are encoded by a large gene family predicted to include at least 20 isoforms in humans. Most mammalian Cx genes consist of two exons. The first consists of untranslated sequence, and the second contains the entire coding sequence. Exceptionally, Cx36 and Cx45 contain 3 exons and 2 introns and the third exon contains the coding sequence (Belluardo et al. 1999 ; Jacob and Beyer 2001). Connexins have been divided in two major subgroups, alpha and beta, according to their amino acid sequence similarity (see Bruzzone et al., 2001; Willecke et al., 2002). Alternative names and additional subgroups have been suggested as well. Cx are synthesized by ribosomes in the endoplasmic reticulum (ER) membrane. All Cx proteins contain four trans-membrane domains (TM1 to TM4), two extracellular loops (E1 and E2) and one cytoplasmic loop. The amino- and carboxyl termini are located in the cytosol (reviewed in Segretain and Falk, 2004). After targeting to the ER, connexins are checked by a quality ...
Connexins (Cxs) are encoded by a large gene family predicted to include at least 20 isoforms in humans. Most mammalian Cx genes consist of two exons. The first consists of untranslated sequence, and the second contains the entire coding sequence. Exceptionally, Cx36 and Cx45 contain 3 exons and 2 introns and the third exon contains the coding sequence (Belluardo et al. 1999 ; Jacob and Beyer 2001). Connexins have been divided in two major subgroups, alpha and beta, according to their amino acid sequence similarity (see Bruzzone et al., 2001; Willecke et al., 2002). Alternative names and additional subgroups have been suggested as well. Cx are synthesized by ribosomes in the endoplasmic reticulum (ER) membrane. All Cx proteins contain four trans-membrane domains (TM1 to TM4), two extracellular loops (E1 and E2) and one cytoplasmic loop. The amino- and carboxyl termini are located in the cytosol (reviewed in Segretain and Falk, 2004). After targeting to the ER, connexins are checked by a quality ...
In humans, connexins (Cxs) and pannexins (Panxs) are the building blocks of hemichannels. These proteins are frequently altered in neoplastic cells and have traditionally been considered as tumor suppressors. Alteration of Cxs and Panxs in cancer cells can be due to genetic, epigenetic and post-transcriptional/post-translational events. Activated hemichannels mediate the diffusional membrane transport of ions and small signaling molecules. In the last decade hemichannels have been shown to participate in diverse cell processes including the modulation of cell proliferation and survival. However, their possible role in tumor growth and expansion remains largely unexplored. Herein, we hypothesize about the possible role of hemichannels in carcinogenesis and tumor progression. To support this theory, we summarize the evidence regarding the involvement of hemichannels in cell proliferation and migration, as well as their possible role in the anti-tumor immune responses. In addition, we discuss the evidence
We have shown previously that postnatal cardiac-restricted deletion of N-cadherin leads to complete dissolution of the intercalated disc structure with a modestly dilated cardiomyopathy.21 We noted sudden death in a majority of animals ≈6 to 8 weeks after inducing deletion of N-cadherin in the heart that was correlated with the onset of spontaneous ventricular arrhythmias. The mechanism by which depleting N-cadherin creates a substrate for ventricular arrhythmogenesis and sudden death in this model is not entirely clear, but is likely related to loss of functional gap junctions.. In line with the role of connexins contributing to the arrhythmogenic substrate, the more comprehensive EP analysis presented in the current study reveals striking similarities between the phenotypes of Cx43 CKO models generated by other groups10,11 and our N-cadherin CKO mice. Surface ECG analysis shows that the QRS amplitude is significantly reduced in N-cadherin CKO mice, similar to that seen in Cx43 CKO mice.10,28 ...
Gap junctions (GJs) are intercellular channels connecting the cytoplasm of adjacent cells. This type of connection is an efficient way of cellular communications in many tissues including the central nervous system. Connexins are the proteins that constitute mammalian GJs, and Connexin43 (Cx43) is the most abundant isoform expressed in body cells. Cx43 has been detected within immature neural populations, but only in astrocytes in the adult brain and investigations have shown that Cx43 channel and adhesive properties largely influence neuronal differentiation of mouse neural progenitor (NP) cells. To date the role of Cx43 in neuronal differentiation remains unexplored in human systems, hence our study aimed to investigate the Cx43 participation in human NP differentiation. We largely detected Cx43 protein within the immature neural populations showing that protein expression occurred by fibroblast growth factor (FGF _2) stimulation through the ERKlj2 pathway; FGF _2 withdrawal induced NP ...
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Purpose: : Oculodentodigital dysplasia (ODDD) is characterized by ocular abnormalities including microphthalmia, enophthalmia, iris malformation and microcornea. A recent clinical report (Gabriel et al, 2011. Arch Ophthalmol 129: 781) examined two ODDD patients and found optic nerve and retinal aberrations not emphasized previously. Also, ciliary body cysts in one patient had not been associated with human ODDD previously. Gja1Jrt/+ mice, a mimic of human ODDD, have ciliary body cysts and retinal abnormalities (Tsui et al. IOVS 52:3539). Gja1Jrt/+ mice carry a glycine to serine substitution at position 60 (G60S) in connexin43, the product of the gap junction alpha 1 (Gja1) gene. Connexins form gap junctions between cells in multiple structures of the eye: ciliary body, lens, iris and retina. The purpose of this project was to show the high prevalence of retinal aberrations in older ODDD mice and the correlation between anterior segment phenotype and the mutant domain of the protein. Methods: : ...
This gene encodes a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Mutations in this gene have been associated with atherosclerosis and a higher risk of myocardial infarction. [provided by RefSeq, Jul 2008] ...
The major risk factors for atherosclerosis are aging, hypertension, hyperlipidemia, smoking, and diabetes. These conditions influence endothelium biology. ECs display GJs, and connexin expression is tightly regulated. Deregulation can occur in different pathological conditions that will be discussed here.. Aging seems to induce a general decrease in connexin expression, with Cx40 being relatively undisturbed for a long time (138). Nicotine induces a decrease in Cx43 expression due to an enhanced protein degradation (121).. Hypertension is a cause of ECs dysfunction and a major risk factor of atherosclerosis. Hypertensive rats have a reduced endothelial expression of Cx37 and Cx43, but Cx40 expression is not modified (141). Moreover, carvedilol, a commonly used β-blocker for hypertension and cardioprotection, directly upregulates endothelial Cx43 independently of its antioxidant activity (141).. Oxidation products of lipoprotein-derived phospholipids upregulate Cx43 and downregulate Cx37 but do ...
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The membrane-permeabilizing action of ATP (formation of a transmembrane pathway for flux of moderately sized molecules) first described as mediated by the so-called purinergic P2Z receptor (20) was later identified as being due to P2X7R (33, 47). The physical relationship between the P2X7R cation channel and the nonselective pore was until very recently unclear. Several models for pore formation have been proposed to explain the somewhat variable degree of agonist-induced permeabilization among various cell types; these include the recruitment of monomeric channel subunits (12, 13, 48) and the recruitment of a lytic pore (34), which has been recently suggested to be Panx1 (30, 38).. Pannexins are a newly discovered (but phylogenetically old) group of proteins that share no sequence homology with the vertebrate gap junction proteins, connexins, and a low but significant homology with the nonchordate gap junction proteins, the innexins (5, 35, 36, 52). When expressed in Xenopus oocytes, Panx1 and ...
Sigma-Aldrich offers abstracts and full-text articles by [Anna R Moore, Wen-Liang Zhou, Carissa L Sirois, Glenn S Belinsky, Nada Zecevic, Srdjan D Antic].
Activation of the inflammasome, a complex that processes interleukin-1β (IL-1β), occurs in response to activation of the adenosine triphosphate receptor P2X7 on macrophages. Activation of P2X7 also triggers the opening of a nonselective, large pore in the plasma membrane. Pelegrin and Surprenant found that pannexin-1 (panx1), a protein that produces hemichannel currents when ectopically expressed in oocytes, was present in monocytes, macrophages, astrocytes, and various cell lines. Panx1, when expressed in transfected HEK cells, coimmunoprecipitated with the P2X7 receptor and colocalized with the P2X7 receptors in ATP-stimulated cells. Using either an siRNA to knock down panx1 or a peptide inhibitor to block the pore function of panx1, the authors showed that dye uptake (a measure of pore opening) in response to P2X7 required panx1. When overexpressed in cells that lack P2X7 receptors, panx1 caused constitutive dye uptake, and when overexpressed in cells that contain P2X7 receptors, panx1 ...
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Phosphorylation of wt or mutant Cx43 in v-Src-expressing cells. (A) Immunoprecipitation of Cx43. Confluent cells were metabolically labeled with 32Pi. Cx43 wa
Hello everybody Im a second year student of molecular biology, and have just startet on a project about connexins and their assembly into connexons. In my readings I find that Triton X-100 soulubility is used to tell something about the proteins, but what? Can anyone in this newsgroup please tell me what the TX-100 soulubility is good for. Has it got something to do with phosphorylation of the proteins? Thanks Ulrik ...
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This week we had 3 inx pairs give. No phenotype were observed and RFP was unsortable at d6 when attempted. Results for inx screen are inconclusive. ...
Formation of platelet plug initiates hemostasis at sites of vascular injury, and triggers pathological thrombosis in ischemic tissue disease. Although various crucial molecules for platelet function have been identified in recent years, the mechanisms of inter- and intra-cellular signaling leading to the formation of a stable platelet plug is still poorly understood. Connexins form gap junctions, clusters of intercellular channels that are known to synchronize responses in multi-cellular organisms through the direct exchange of ions, small metabolites and other second messenger molecules between adjacent cells. Here, we report the expression of the gap junction protein connexin37 (Cx37) in mouse and human platelets. In addition, we observed functional gap junction communication between platelets during platelet aggregation in vitro, as assessed by microinjection of the gap junction-permeable tracer neurobiotin in platelets isolated from human or wild-type mice. In contrast, the tracer did not ...
The biogenesis of connexins and their assembly into functional gap junction hemichannels (connexons) was studied with the use of a cell-free transcription/translation system. Velocity sedimentation on sucrose gradients showed that a small proportion of connexin (Cx) 26 and Cx32 that were co-translationally translocated into microsomes were oligomers of Cx26 and Cx32. Chemical cross-linking studies showed that these corresponded to hexameric connexons. Reconstitution of connexons synthesized in vitro into liposomes induced permeability properties consistent with the view that open gap junction hemichannels were produced. By using an immunoprecipitation approach, a simultaneous translation of Cx26 and Cx32 incorporated into microsomes resulted in homomeric connexons. However, supplementation of the translation system in vitro with liver Golgi membranes produced heteromeric connexons constructed of Cx32 and Cx26, and also resulted in an increased oligomerization especially of Cx32. All of the ...
TY - JOUR. T1 - Coincidence of mutations in different connexin genes in Hungarian patients. AU - Tóth, Tímea. AU - Kupka, Susan. AU - Haack, Birgit. AU - Fazakas, Ferenc. AU - Muszbek, LáSzló. AU - Blin, Nikolaus. AU - Pfister, Markus. AU - Sziklai, István. PY - 2007/9. Y1 - 2007/9. N2 - Mutations in the GJB2 gene are the most common cause of hereditary prelingual sensorineural hearing impairment in Europe. Several studies indicate that different members of the connexin protein family interact to form gap junctions in the inner ear. Mutations in different connexin genes may accumulate and, consequently lead to hearing impairment. Therefore, we screened 47 Hungarian GJB2-heterozygous (one mutation in coding exon of the GJB2 gene) patients with hearing impairment for DNA changes in two further connexin genes (GJB6 and GJB3) and in the 5′ non-coding region of GJB2 including the splice sites. Eleven out of 47 GJB2-heterozygous patients analyzed carried the splice site mutation -3170G,A in the ...
TY - JOUR. T1 - Gap junctional channels regulate acid secretion in the mammalian gastric gland. AU - Radebold, K.. AU - Horakova, E.. AU - Gloeckner, J.. AU - Ortega, G.. AU - Spray, David C.. AU - Vieweger, H.. AU - Siebert, K.. AU - Manuelidis, L.. AU - Geibel, J. P.. PY - 2001/10/1. Y1 - 2001/10/1. N2 - Gap junction channels are regarded as a primary pathway for intercellular message transfer, including calcium wave propagation. Our study identified two gap junctional proteins, connexin26 and connexin32, in rat gastric glands by RT-PCR, Western blot analysis, and immunofluorescence. We demonstrated a potential physiological role of the gap junctional channels in the acid secretory process using the calcium indicator fluo-3, and microinjection of Lucifer Yellow. Application of gastrin (10-7 M) to the basolateral membrane resulted in the induction of uniphasic calcium signals in adjacent parietal cells. In addition, single parietal cell microinjections in intact glands with the cell-impermeant ...
Methods and results - Thirty New Zealand rabbits were randomly divided into three experimental groups: myocardial infarction, carvedilol and control groups. The left anterior descending coronary artery was ligated in animals in the myocardial infarction group; in the control animals no artery was ligated. The animals in the carvedilol group were administered carvedilol by way of gavages at a dose of 0.5 mg/kg. After the experiment had gone on for 8 weeks, the spatial distribution and the amount of gap junction protein connexin 40 in the left auricle ware measured by fluorescence immunohistochemistry and Western blot, respectively. Compared with the controls, the amount of left atrial appendage gap junction protein connexin 40 in the myocardial infarction group was significantly decreased (P < 0.01), and an uneven distribution of gap junction protein connexin 40 was markedly observed. The amount of gap junction protein connexin 40 in the carvedilol group was higher than that in the myocardial ...
Gap junctions are clusters of specialized intercellular channels that regulate the direct exchange of ions and various hydrophilic cellular metabolites that are smaller than 1000 Da, a process known as gap junctional intercellular communication (GJIC) (Alexander and Goldberg, 2003). Two inter-docked connexons (hemichannels), one from each of two apposing cells, form a functional gap junction channel. Each connexon is composed of six oligomerized connexin (Cx) subunits, and, to date, the connexin family consists of 21 members in human (Söhl and Willecke, 2003; Söhl and Willecke, 2004). Interestingly, the primary function of gap junction channels is to facilitate intercellular communication; however, hemichannels have also been reported to exist and function at the cell surface in an undocked state, permitting the transfer of molecules between extracellular and intracellular environments (Anselmi et al., 2008; Burra and Jiang, 2011; Tong et al., 2007). Hemichannels that are formed from single or ...
Cxs (connexins), the protein subunits forming gap junction intercellular communication channels, are transported to the plasma membrane after oligomerizing into hexameric assemblies called connexin hemichannels (CxHcs) or connexons, which dock head-to-head with partner hexameric channels positioned on neighbouring cells. The double membrane channel or gap junction generated directly couples the cytoplasms of interacting cells and underpins the integration and co-ordination of cellular metabolism, signalling and functions, such as secretion or contraction in cell assemblies. In contrast, CxHcs prior to forming gap junctions provide a pathway for the release from cells of ATP, glutamate, NAD+ and prostaglandin E2, which act as paracrine messengers. ATP activates purinergic receptors on neighbouring cells and forms the basis of intercellular Ca2+ signal propagation, complementing that occuring more directly via gap junctions. CxHcs open in response to various types of external changes, including ...
TY - JOUR. T1 - Impaired trafficking of connexins in androgen-independent human prostate cancer cell lines and its mitigation by α-catenin. AU - Govindarajan, Rajgopal. AU - Zhao, Sumin. AU - Song, Xiao Hong. AU - Guo, Rong Jun. AU - Wheelock, Margaret. AU - Johnson, Keith R.. AU - Mehta, Parmender P. PY - 2002/12/20. Y1 - 2002/12/20. N2 - Gap junctions, composed of connexins, provide a pathway of direct intercellular communication for the diffusion of small molecules between cells. Evidence suggests that connexins act as tumor suppressors. We showed previously that expression of connexin-43 and connexin-32 in an indolent prostate cancer cell line, LNCaP, resulted in gap junction formation and growth inhibition. To elucidate the role of connexins in the progression of prostate cancer from a hormone-dependent to -independent state, we introduced connexin-43 and connexin-32 into an invasive, androgen-independent cell line, PC-3. Expression of these proteins in PC-3 cells resulted in intracellular ...
Purpose: To screen for mutations of connexin50 (Cx50)/GJA8 in a panel of patients with inherited cataract and to determine the cellular and functional consequences of the identified mutation.. Methods: All patients in the study underwent a full clinical examination and leucocyte DNA was extracted from venous blood. The GJA8 gene was sequenced directly. Connexin function and cellular trafficking were examined by expression in Xenopus oocytes and HeLa cells.. Results: Screening of the GJA8 gene identified a 139 G to A transition that resulted in the replacement of aspartic acid by asparagine (D47N) in the coding region of Cx50. This change co-segregated with cataract among affected members of a family with autosomal dominant nuclear pulverulent cataracts. While pairs of Xenopus oocytes injected with wild type Cx50 RNA formed functional gap junction channels, pairs of oocytes injected with Cx50D47N showed no detectable intercellular conductance. Co-expression of Cx50D47N did not inhibit gap ...
My research interests focus on gap junctions which are involved in cell-to-cell communication. Regulating the chemical and physical properties of gap junctions are the different connexin proteins. Unique communication compartments can be formed when gap junctions are assembled from various connexins.. Presently, I am examining the implications of gap junctions on cell differentiation and development using the testis as a model. Organized in the seminiferous tubule and supported by Sertoli cells are some 63 different germ cell types. The germ cells are arranged and organized in the seminiferous epithelium for an ordered development and differentiation into spermatozoa. We are currently determining gap junctions role in the formation of specific communication compartments and how gap junctions regulate and support specific spermatogenic cells. Gap junction assembly, connexin composition, and the chemical and physical properties of homotypic - heterotypic gap junctions will be examined ...
Mutations in the gap junction geneconnexin32(Cx32) cause the X-linked form of Charcot-Marie-Tooth disease, an inherited demyelinating neuropathy. More than 130 different mutations have been described, affecting all portions of the Cx32 protein. In transfected cells, the mutant Cx32 proteins encoded by someCx32mutations fail to reach the cell surface; other mutant proteins reach the cell surface, but only one of these forms functional gap junctions. In peripheral nerve, Cx32 is localized to incisures and paranodes, regions of noncompact myelin within the myelin sheath. This localization suggests that Cx32 forms
Early descriptions of gap junctions and connexons did not refer to them as such and many other terms were used. It is likely that synaptic disks[117] were an accurate reference to gap junction plaques. While the detailed structure and function of the connexon was described in a limited way at the time the gross disk structure was relatively large and easily seen by various TEM techniques. Disks allowed researchers using TEM to easily locate the connexons contained within the disk like patches in vivo and in vitro. The disk or plaque appeared to have structural properties different from those imparted by the connexons alone.[26] It was thought that if the area of membrane in the plaque transmitted signals the area of membrane would have to be sealed in some way to prevent leakage.[118] Later studies showed gap junction plaques are home to non-connexin proteins making the modern usage of the terms gap junction and gap junction plaque non-interchangeable as the area of the gap ...
Early descriptions of gap junctions and connexons did not refer to them as such and many other terms were used. It is likely that synaptic disks[116] were an accurate reference to gap junction plaques. While the detailed structure and function of the connexon was described in a limited way at the time the gross disk structure was relatively large and easily seen by various TEM techniques. Disks allowed researchers using TEM to easily locate the connexons contained within the disk like patches in vivo and in vitro. The disk or plaque appeared to have structural properties different from those imparted by the connexons alone.[25] It was thought that if the area of membrane in the plaque transmitted signals the area of membrane would have to be sealed in some way to prevent leakage.[117] Later studies showed gap junction plaques are home to non-connexin proteins making the modern usage of the terms gap junction and gap junction plaque non-interchangeable as the area of the gap ...
Guys, Ive uploaded my disease stuff except im having problems with uploading the references and pictures. WIll try again later. Ive also added a few things to our glossary. Anyway hope youve all had a good break! --Elizabeth Blanchard 10:28, 30 April 2011 (EST) I found another article concerning disease that might be of use: Gap-Junction Channels Dysfunction in Deafness and Hearing Loss I wouldnt put the abstract since its too long. [1] --z3283837 23:00, 26 April 2011 (EST) Hey guys, I am kind of finished with my part for the intro and the function although it needs a little bit of touch up. Anyway, while researching, I just found a few review articles that might be helpful. Whoever is doing the location of gap junctions, this article below gives you an overview of the expression patterns of different connexins in different tissues. Diversity and properties of connexin gap junction channels Gap junction channels are composed of two apposing hemichannels (connexons) in the contiguous cells ...
Guys, Ive uploaded my disease stuff except im having problems with uploading the references and pictures. WIll try again later. Ive also added a few things to our glossary. Anyway hope youve all had a good break! --Elizabeth Blanchard 10:28, 30 April 2011 (EST) I found another article concerning disease that might be of use: Gap-Junction Channels Dysfunction in Deafness and Hearing Loss I wouldnt put the abstract since its too long. [1] --z3283837 23:00, 26 April 2011 (EST) Hey guys, I am kind of finished with my part for the intro and the function although it needs a little bit of touch up. Anyway, while researching, I just found a few review articles that might be helpful. Whoever is doing the location of gap junctions, this article below gives you an overview of the expression patterns of different connexins in different tissues. Diversity and properties of connexin gap junction channels Gap junction channels are composed of two apposing hemichannels (connexons) in the contiguous cells ...
TY - JOUR. T1 - Extracellular loop cysteine mutant of Cx37 fails To suppress proliferation of rat insulinoma cells. AU - Good, Miranda E.. AU - Ek-Vitorín, José F.. AU - Burt, Janis M.. PY - 2012/7. Y1 - 2012/7. N2 - Although a functional pore domain is required for connexin 37 (Cx37)-mediated suppression of rat insulinoma (Rin) cell proliferation, it is unknown whether functional hemichannels would be sufficient or if Cx37 gap junction channels are required for growth suppression. To test this possibility, we targeted extracellular loop cysteines for mutation, expecting that the mutated protein would retain hemichannel, but not gap junction channel, functionality. Cysteines at positions 61 and 65 in the first extracellular loop of Cx37 were mutated to alanine and the mutant protein (Cx37-C61,65A) expressed in Rin cells. Although the resulting iRin37-C61,65A cells expressed the mutant protein comparably to Cx37 wild-type (Cx37-WT)-expressing Rin cells (iRin37), Cx37-C61,65A expression did not ...
TY - JOUR. T1 - A role for an inhibitory connexin in testis?. AU - Chang, Michelle. AU - Werner, Rudolf. AU - Dahl, Gerhard. N1 - Funding Information: The expert technical help by Audrey Llanes is appreciated. This work was supported by National Institutes of Health grants GM48610 (to G.D.) and GM40583 (to R.W.).. PY - 1996/4/10. Y1 - 1996/4/10. N2 - Functional expression of gap junction proteins can be obtained conveniently with the paired oocyte cell-cell channel assay. So far all gap junction proteins (connexins), with the exception of one, have been found to make: functional channels either by themselves or as hybrid channels (two hemichannels of different connexin composition). Connexin33 (cx33) appears not to follow this rule. Expression of cx33 in oocytes does not yield functional channels, and attempts to identify another connexin with which cx33 can form hybrid channels have failed so far. The observation was made that cx33 inhibits functional expression of other connexins in a ...
Gap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two hemichannels, each containing six connexins, contributed by each neighboring cell. These channels permit the direct transfer of small molecules including ions, amino acids, nucleotides, second messengers and other metabolites between adjacent cells. Gap junctional communication is essential for many physiological events, including embryonic development, electrical coupling, metabolic transport, apoptosis, and tissue homeostasis. Communication through Gap Junction is sensitive to a variety of stimuli, including changes in the level of intracellular Ca2+, pH, transjunctional applied voltage and phosphorylation/dephosphorylation processes. This figure represents the possible activation routes of different protein kinases involved in Cx43 and Cx36 phosphorylation ...
Gap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two hemichannels, each containing six connexins, contributed by each neighboring cell. These channels permit the direct transfer of small molecules including ions, amino acids, nucleotides, second messengers and other metabolites between adjacent cells. Gap junctional communication is essential for many physiological events, including embryonic development, electrical coupling, metabolic transport, apoptosis, and tissue homeostasis. Communication through Gap Junction is sensitive to a variety of stimuli, including changes in the level of intracellular Ca2+, pH, transjunctional applied voltage and phosphorylation/dephosphorylation processes. This figure represents the possible activation routes of different protein kinases involved in Cx43 and Cx36 phosphorylation ...
TY - JOUR. T1 - A novel missense mutation in the second extra cellular domain of GJB2, p.Ser183Phe, causes a syndrome of focal palmoplantar keratoderma with deafness. AU - de Zwart-Storm, E. A.. AU - van Geel, M.. AU - van Neer, P. A.F.A.. AU - Steijlen, P. M.. AU - Martin, Patricia E.M.. AU - van Steensel, M. A.M.. N1 - Originally published in: American Journal of Pathology (2008), 173 (4), pp.1113-11179.. PY - 2008/10/1. Y1 - 2008/10/1. N2 - Gap junctions, which consist of connexins, are intercellular channels that mediate rapid intercellular communication. In the skin, connexins are involved in the regulation of epidermal growth and differentiation. GJB2 encodes connexin26, which is an important skin-expressed gap junction protein. Mutations in GJB2 cause a wide variety of unique disorders, but despite extensive research, their mechanisms of action are poorly understood. The identification of novel diseases caused by mutations in GJB2 may help to illuminate the genotype-phenotype correlation ...
Objective: Gap junctions (formed by connexins, Cx) are important for functional coordination of cells in the vascular wall. However, little is known about their physiological regulation in this tissue. We examined the effects of nitric oxide (NO), an important mediator of vasomotion, wound healing and angiogenesis, on the formation of gap junctions in endothelial cells (human umbilical vein endothelial cells, HUVEC). Methods: Flow cytometry was used to determine dye transfer through newly formed gap junctions between acutely coincubated HUVECs. Parallel experiments in wild-type HeLa cells (no connexins) and transfected HeLa cells exclusively expressing Cx43, Cx40 or Cx37 were performed to determine the specific role of Cx subtypes. The intracellular distribution of Cx40 was examined after fractionation with triton by Western blotting. Intracellular levels of cGMP and cAMP were measured by radioimmunoassay. Results: The NO donor SNAP (1 μM) enhanced gap-junctional coupling in HUVECs by about ...
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Gap junction channels formed by alpha3 (Cx46) and alpha8 (Cx50) connexin provide pathways for communication between the fiber cells in the normal transparent lens. To determine the specific role of alpha3 connexin in vivo, the alpha3 connexin gene was disrupted in mice. Although the absence of alpha …
Mouse Connexin-23 ELISA Kit;Mouse Cx23 ELISA Kit;Mouse AEY12 ELISA Kit;Mouse D230044M03Rik ELISA Kit;Mouse Gjf1 ELISA Kit;Mouse Gsfaey12 ELISA Kit;Mouse gap junction protein, epsilon 1 ELISA Kit;Mouse gap junction epsilon-1 protein ELISA Kit;Mouse connexin 23 ELISA Kit;Mouse putative gap junction protein connexin Cx43.4 ELISA Kit ...
Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP(3), and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is ...
Our results demonstrate changes of gap junction channel characteristics and alterations in the pathways of intercellular communication in the organ of Corti during postnatal development. The characteristics of early postnatal GJIC bear little resemblance to those in the hearing cochlea. These observations have implications for the interpretation of studies of GJIC in normal hearing and disease. We have provided functional evidence for the existence of gap junction channels comprising heteromeric Cx26/Cx30 connexons in native cochlear tissue in hearing animals based on the selective transfer of diagnostic dyes, in conjunction with the colocalization of Cx26 and Cx30 within supporting cells. We found evidence for Cx26-only channels (i.e., LY permeable) only in peripheral supporting cells within the organ of Corti in hearing animals (supplemental Fig. 4, available at www.jneurosci.org as supplemental material). Furthermore, we have provided functional and anatomical evidence that is consistent with ...
We examined changes in the expression and localization of connexin proteins and transcripts by means of immunofluorescence and in situ hybridization in normal conditions, wound healing and carcinogenesis using hamster tongue epithelium, in which differentiation, migration and growth of keratinocytes takes place physiologically and pathologically. In normal hamster tongue epithelium, immunofluorescent staining showed that Cx26 and Cx43 proteins were localized differently during differentiation of keratinocytes, but in in situ hybridization, the localization of Cx26 and Cx43 transcripts overlapped considerably, suggesting that the different localization of Cx26 and Cx43 proteins in squamous epithelium is largely regulated at post-transcriptional levels. During wound healing, the expression and localization of connexin proteins and transcripts were changed drastically. Shortly (6 h) after injury the expression of Cx26 and Cx43 proteins decreased at wound edges, but by 1-3 days after injury the ...
MIM *0608803 Alternative titles; symbols •GAP JUNCTION PROTEIN, ALPHA 12; GJA12 •GAP JUNCTION PROTEIN, 47-KD •CONNEXIN 47; CX47 CONNEXIN 46.6; CX46.6 Gene map locus: 1q41-q42 Text For background information on connexins, see CX26 (GJB2; 121011). Cloning The complete coding sequence of the GJA12 gene has been deposited in GenBank (AF014643). The GJA12 sequence encodes a 436-amino acid protein (GenBank AAB94511). Gene Function Gap junction proteins are members of a large family of homologous connexins and comprise 4 transmembrane, 2 extracellular, and 3 cytoplasmic domains. They have been identified in a broad range of mammalian tissues, and most tissues expressed more than 1 species of connexin protein.Menichella et al. (2003) found that Cx47 (Gja12) is expressed specifically in oligodendrocytes and that its expression is regulated in parallel with other myelin genes. Cx47 and Cx32 (Gjb1; 304040) partially colocalized in oligodendrocytes, which together with Schwann cells synthesize the ...
Apoptotic cells release the nucleotides ATP and UTP to attract phagocytic cells, which in turn clear the apoptotic cells. Chekeni et al. found that carbenoxolone (CBX), which inhibits connexins (which form gap junctions) and pannexins (which form plasma membrane channels), and probenicid, which is thought to be more specific for pannexins, reduced ATP release from apoptotic Jurkat cells to a similar extent as the caspase inhibitor zVAD (which blocks the release of ATP from apoptotic cells). Small interfering RNAs (siRNAs) directed against pannexin 1 (PANX1) decreased the release of ATP and UTP from apoptotic Jurkat cells but did not prevent apoptosis. Supernatant from PANX1 siRNA-transfected apoptotic cells recruited fewer monocytes in an in vitro assay of cell migration and when placed in a subcutaneous air pouch in mice. In contrast, Jurkat cells stably overexpressing PANX1 released more ATP and UTP, and supernatants from these cells (after apoptosis had been induced) recruited more monocytes ...
Fibroblasts play a significant role in the development of electrical and mechanical dysfunction of the heart; however, the underlying mechanisms are only partially understood. One widely studied mechanism suggests that fibroblasts produce excess extracellular matrix, resulting in collagenous septa t …
Gap junctions allow intercellular communication. Their structural subunits are four-transmembrane proteins named connexins (Cxs), which can be post-transcriptionally regulated by developmental and cellular signalling cues. Cx translation and mRNA stability is regulated by miRNAs and RNA-binding proteins (RBPs) such as human antigen R (HuR). In addition, several Cxs have also been suggested to contain 5′ internal ribosome entry site (IRES) elements that are thought to allow cap-independent translation in situations such as mitosis, stress and senescence. Furthermore, several recent reports have documented internal translation of Cx mRNAs that result in N-terminally truncated protein isoforms that may have unique gap junction-independent functions [Ul-Hussain et al. (2008) BMC Mol. Biol. 9, 52; Smyth and Shaw (2013) Cell Rep. 5, 611-618; Salat-Canela et al. (2014) Cell Commun. Signal. 12, 31; Ul-Hussain et al. (2014) J. Biol. Chem. 289, 20979-20990]. This review covers the emerging field of the ...
Cardiac myocytes and fibroblasts form extensive networks in the heart, with numerous anatomical contacts between cells. Fibroblasts, obligatory components of the extracellular matrix, represent the majority of cells in the normal heart, and their number increases with aging and during disease. The myocyte network, coupled by gap junctions, is generally believed to be electrically isolated from fibroblasts in vivo. In culture, however, the heterogeneous cell types form functional gap junctions, which can provide a substrate for electrical coupling of distant myocytes, interconnected by fibroblasts only. Whether similar behavior occurs in vivo has been the subject of considerable debate. Recent electrophysiological, immunohistochemical, and dye-coupling data confirmed the presence of direct electrical coupling between the two cell types in normal cardiac tissue (sinoatrial node), and it has been suggested that similar interactions may occur in post-infarct scar tissue. Such heterogeneous cell ...
HeLa cells seem not to be junctionally coupled when probed with techniques such as Lucifer yellow spreading and/or ionic coupling measured with three inserted microelectrodes. When investigated with double whole-cell patch-clamp measurements, HeLa cells in monolayer cultures were electrically coupled in 39% of the cases with very low transjunctional conductances (average one to five open channels). These gapjunction channels had a single-channel conductance γ=26±6 pS and were voltage-gated with an equivalent gating charge ζ=3.1±1.5 for a voltage of half-maximal inactivation Uo=49±10 mV. The voltage-dependent component represents only 31±8% of the total junctional conductance. The voltage-insensitive conductance is characterized by a residual open probability po(∞)=0.34±0.12, which corresponds to a ratio Gmin/Gmax=0.50±0.12. Dissociation of monolayer cells into cell pairs yielded about 58% coupled cell pairs with no notably altered single-channel properties ...
The progressive death of retinal ganglion cells and resulting visual deficits are hallmarks of glaucoma, but the underlying mechanisms remain unclear. In many neurodegenerative diseases, cell death induced by primary insult is followed by a wave of secondary loss. Gap junctions (GJs), intercellular channels composed of subunit connexins, can play a major role in secondary cell death by forming conduits through which toxic molecules from dying cells pass to and injure coupled neighbors. Here we have shown that pharmacological blockade of GJs or genetic ablation of connexin 36 (Cx36) subunits, which are highly expressed by retinal neurons, markedly reduced loss of neurons and optic nerve axons in a mouse model of glaucoma. Further, functional parameters that are negatively affected in glaucoma, including the electroretinogram, visual evoked potential, visual spatial acuity, and contrast sensitivity, were maintained at control levels when Cx36 was ablated. Neuronal GJs may thus represent potential ...
While a number of different gap junction proteins have now been identified, hepatic gap junctions are unique in being the first demonstrated case where two homologous, but distinct, proteins (28,000 and 21,000 Mr) are found within a single gap junctional plaque (Nicholson, B. J., R. Dermietzel, D. Teplow, O. Traub, K. Willecke, and J.-P. Revel. 1987. Nature [Lond.]. 329:732-734). The cDNA for the major 28,000-Mr component has been cloned (Paul, D. L. 1986. J. Cell Biol. 103:123-134) (Kumar, N. M., and N. B. Gilula. 1986. J. Cell Biol. 103:767-776) and, based on its deduced formula weight of 32,007, has been designated connexin 32 (or Cx32 as used here). We now report the selection and characterization of clones for the second 21,000-Mr protein using an oligonucleotide derived from the amino-terminal protein sequence. Together the cDNAs represent 2.4 kb of the single 2.5-kb message detected in Northern blots. An open reading frame of 678 bp coding for a protein with a calculated molecular mass of ...
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Neuronal gap junctions are pervasive in structures of the CNS during development. As our results demonstrate, the TRN is no exception. In fact, during the first postnatal week the other major category of thalamic neurons-thalamocortical relay cells-are also coupled by gap junctions (Lee et al., 2006), as are their targets, pyramidal cells and spiny stellate cells of the neocortex (Connors et al., 1983; Lo Turco and Kriegstein, 1991; Yuste et al., 1992). Unlike the principal neurons of both rodent thalamus and neocortex, however, TRN neurons and inhibitory interneurons of the neocortex (Galarreta and Hestrin, 1999, 2002; Gibson et al., 1999) remain coupled after the early postnatal period. This striking divergence suggests different functions for the gap junctions of immature and mature neurons in the thalamus.. Gap junction channels have been implicated in a variety of tasks, including intercellular signaling with electrical (ionic) current, passage of intercellular chemical messengers, ...
Yancey, S. Barbara and Biswal, Sandip and Revel, Jean-Paul (1992) Spatial and temporal patterns of distribution of the gap junction protein connexin43 during mouse gastrulation and organogenesis. Development, 114 (1). pp. 203-212. ISSN 0950-1991. http://resolver.caltech.edu/CaltechAUTHORS:YANdev92 ...
Wu, C.-L., Shih, M.-F. M., Lai, J. S.-Y., Yang, H.-T., Turner, G. C., Chen, L. , Chiang, A. S. (2011) Heterotypic Gap Junctions between Two Neurons in the Drosophila Brain Are Critical for Memory. Current Biology, 21 (10). pp. 848-854. ISSN 0960-9822 ...
We have discovered a requirement for a novel connexin gene (frm-cx) in specification of the anterior neural plate in the invertebrate chordate Ciona. (The conne...
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In agreement with previous reports (11, 13, 18, 26, 44), the present data indicate that connexin mimetic peptides inhibit the formation of gap junction channels by binding to their target sequence, the connexins. However, the peptides did not have an acute effect on the nonjunctional membrane channels formed by the connexin chimera used in this study. Only over a time span of hours, a retardation of the typical increase in membrane conductance was observed. This slow effect is inconsistent with a gating mechanism of the channel and is even too slow to account for alteration of channel activity due to peptide-induced secondary modifications of the protein. Instead, the time course is consistent with the life-time of the protein, and it is thus conceivable that the bound peptide tags the protein for degradation.. All three connexin mimetic peptides tested here, however, attenuated the currents carried by membrane channels formed by the unrelated protein pannexin1. A scrambled version of the ...
Abrams, Charles K.; Rash, John E. (2009). "Connexins in the Nervous System". In Harris, Andrew; Locke, Darren (eds.). Connexins ...
One connexin protein has four transmembrane domains 6 Connexins create one Connexon (hemichannel). When different connexins ... How the connexins may be transported to the plaques using tubulin is becoming clearer. The formation plaque and non-connexin ... By study of connexins still in membranes lipids associated with the connexins have been studied. It was found that specific ... Connexin proteins expressed in neuronal gap junctions include: mCX36 mCX57 mCX45 with mRNAs for at least five other connexins ( ...
This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of ... 2003). "Comparison of connexin 43, 40 and 45 expression patterns in the developing human and mouse hearts". Cell Commun. Adhes ... Gap junction gamma-1 protein (GJC1), also known as gap junction alpha-7 protein (GJA7) and connexin 45 (Cx45) - is a protein ... "Entrez Gene: GJA7 gap junction protein, alpha 7, 45kDa". Andrew L Harris; Darren Locke (2009). Connexins, A Guide. New York: ...
2004). "Molecular interaction of connexin 30.3 and connexin 31 suggests a dominant-negative mechanism associated with ... Gap junction beta-4 protein (GJB4), also known as connexin 30.3 (Cx30.3) - is a protein that in humans is encoded by the GJB4 ... "Entrez Gene: GJB4 gap junction protein, beta 4". Andrew L Harris; Darren Locke (2009). Connexins, A Guide. New York: Springer. ... 2000). "Mutation in the gene for connexin 30.3 in a family with erythrokeratodermia variabilis". Am. J. Hum. Genet. 67 (5): ...
2004). "Molecular interaction of connexin 30.3 and connexin 31 suggests a dominant-negative mechanism associated with ... This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of ... Gap junction beta-3 protein (GJB3), also known as connexin 31 (Cx31) - is a protein that in humans is encoded by the GJB3 gene ... 2001). "Connexin 31 (GJB3) is expressed in the peripheral and auditory nerves and causes neuropathy and hearing impairment". ...
Connexins are membrane-spanning proteins that assemble to form gap junction channels that facilitate the transfer of ions and ... Most of the mutations of the GJB1 gene switch or change a single amino acid in the gap junction (connexin-32) protein, although ... Gap junction beta-1 protein (GJB1), also known as connexin 32 (Cx32) is a transmembrane protein that in humans is encoded by ... Gap junction beta-1 protein is a member of the gap junction connexin family of proteins that regulates and controls the ...
Connexin 30 has been found to be co-localized with connexin 26. Cx30 and Cx26 have also been found to form heteromeric and ... Connexin 26 and connexin 30 are commonly accepted to be the predominant gap junction proteins in the cochlea. Genetic knockout ... Connexins span the plasma membrane 4 times, with amino- and carboxy-terminal regions facing the cytoplasm. Connexin genes are ... Erbe CB, Harris KC, Runge-Samuelson CL, Flanary VA, Wackym PA (April 2004). "Connexin 26 and connexin 30 mutations in children ...
Connexons are formed by six 7.5 nm long, four-pass membrane-spanning protein subunits called connexins, which may be identical ... Andrew L. Harris; Darren Locke (2009). Connexins, a guide. New York: Springer. p. 574. ISBN 978-1-934115-46-6. Haas, Julie S.; ...
The connexin-43 internal ribosome entry site is an RNA element present in the 5' UTR of the mRNA of GJA1. This internal ... Gap junction alpha-1 protein (GJA1), also known as connexin 43 (Cx43), is a protein that in humans is encoded by the GJA1 gene ... GJA1 is the most ubiquitously expressed connexin and is detected in most cell types. It is the major protein in heart gap ... Vliagoftis H, Ebeling C, Ilarraza R, Mahmudi-Azer S, Abel M, Adamko D, Befus AD, Moqbel R (2014). "Connexin 43 expression on ...
1998). "Assembly of connexins and MP26 in lens fiber plasma membranes studied by SDS-fracture immunolabeling". J. Cell Sci. 111 ... 2002). "Multimeric connexin interactions prior to the trans-Golgi network". J. Cell Sci. 114 (Pt 22): 4013-24. PMID 11739633. ... 2004). "Lens connexins alpha3Cx46 and alpha8Cx50 interact with zonula occludens protein-1 (ZO-1)". Mol. Biol. Cell. 14 (6): ... Andrew L Harris; Darren Locke (2009). Connexins, A Guide. New York: Springer. p. 574. ISBN 978-1-934115-46-6. Hsieh CL, Kumar ...
This is possible due to six connexin proteins interacting to form a cylinder with a pore in the centre called a connexon. The ... Andrew L Harris; Darren Locke (2009). Connexins, A Guide. New York: Springer. p. 574. ISBN 978-1-934115-46-6. Yan HH, Mruk DD, ... Wei CJ, Xu X, Lo CW (2004). "Connexins and cell signaling in development and disease". Annual Review of Cell and Developmental ... Connexon pores vary in size, polarity and therefore can be specific depending on the connexin proteins that constitute each ...
... , also called connexin-36 (CX36), is a member of the connexin gene family that is expressed predominantly in mammalian ... Connexins associate in groups of 6 and are organized radially around a central pore to form connexons. Each gap junction ... Gap junction delta-2 protein (GJD2) also known as connexin-36 (Cx36) or gap junction alpha-9 protein (GJA9) is a protein that ... "Entrez Gene: GJA9 gap junction protein, alpha 9, 36kDa". Andrew L Harris; Darren Locke (2009). Connexins, A Guide. New York: ...
Structurally, pannexins and connexins are very similar, consisting of 4 transmembrane domains, 2 extracellular and 1 ... Probenecid did not affect channels formed by connexins, but it inhibits pannexin-1 channels. Panchin Y, Kelmanson I, Matz M, ... Probenecid, a well-established drug for the treatment of gout, allows for discrimination between channels formed by connexins ... Andrew L Harris & Darren Locke (2009). Connexins, A Guide. New York: Springer. p. 574. ISBN 978-1-934115-46-6.. ...
Connexin types can be further differentiated by using their predicted molecular weight (ex: Connexin 43 is Cx 43 due to its ... In biology, a connexon, also known as a connexin hemichannel, is an assembly of six proteins called connexins that form the ... Connexons made of the same type of connexins are considered homomeric, while connexons made of differing types of connexins are ... forming a hemi-channel that is composed of connexins. Connexins are the smaller protein molecules that make up connexons and ...
Proteins, called connexins, purified from fractions of enriched gap junctions from different tissues differ. The connexins are ... Connexin 26 also plays a role in tumor suppression through mediation of the cell cycle. The abnormal expression of Cx26, ... Gap junction beta-2 protein (GJB2), also known as connexin 26 (Cx26) - is a protein that in humans is encoded by the GJB2 gene ... Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, Mueller RF, Leigh IM (May 1997). "Connexin 26 mutations in ...
1998). "Assembly of connexins and MP26 in lens fiber plasma membranes studied by SDS-fracture immunolabeling". J. Cell Sci. 111 ... Rong P, Wang X, Niesman I, Wu Y, Benedetti LE, Dunia I, Levy E, Gong X (January 2002). "Disruption of Gja8 (alpha8 connexin) in ... 2007). "Connexin 50 gene on human chromosome 1q21 is associated with schizophrenia in matched case control and family-based ... 2004). "Lens connexins alpha3Cx46 and alpha8Cx50 interact with zonula occludens protein-1 (ZO-1)". Mol. Biol. Cell. 14 (6): ...
Harris AL, Locke D (2009). Connexins, a guide. New York: Springer. p. 574. ISBN 978-1-934115-46-6. Haas JS, Zavala B, Landisman ...
Pannexins or Connexins? Chapter 12. In: A. Harris, D. Locke (eds.), Connexins: A Guide doi:10.1007/978-1-59745-489-6_12 Bao L, ... While the connexin family of gap junction proteins was well-characterized in vertebrates, no homologues were found in non- ... Structurally, innexins and connexins are very similar, consisting of 4 transmembrane domains, 2 extracellular and 1 ... Gap junction proteins with no sequence homology to connexins were initially identified in fruit flies. It was suggested that ...
This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of ... Gap junction alpha-5 protein (GJA5), also known as connexin 40 (Cx40) - is a protein that in humans is encoded by the GJA5 gene ... 2003). "Comparison of connexin 43, 40 and 45 expression patterns in the developing human and mouse hearts". Cell Commun. Adhes ... 2002). "Connexin expression in Huntington's diseased human brain". Cell Biol. Int. 22 (11-12): 837-47. doi:10.1006/cbir. ...
This protein, like other Connexin proteins, forms connections between cells known as gap junctions. Connexin 37 can be found in ... Gap junction alpha-4 protein, also known as Connexin-37 or Cx37, is a protein that in humans is encoded by the GJA4 gene. ... Willecke K, Jungbluth S, Dahl E, Hennemann H, Heynkes R, Grzeschik KH (December 1990). "Six genes of the human connexin gene ... Andrew L Harris; Darren Locke (2009). Connexins, A Guide. New York: Springer. p. 574. ISBN 978-1-934115-46-6. Beyer EC, Paul DL ...
Retamal MA (2014). "Connexin and Pannexin hemichannels are regulated by redox potential". Frontiers in Physiology. 5: 80. doi: ... Hemichannels consist of connexins. Pannexins are involved in the process of purinergic signalling. They release adenosine ... Spray DC, Ye ZC, Ransom BR (November 2006). "Functional connexin "hemichannels": a critical appraisal". Glia. 54 (7): 758-73. ... and opens both connexin and pannexin channels, therefore contributing to the propagation of calcium waves across astrocytes and ...
The abnormal distribution of gap junction proteins such as GJA1 (also known as Connexin 43), and GJA5 (Connexin 40) causes non- ... Saffitz JE (2006). "Connexins, conduction, and atrial fibrillation". N. Engl. J. Med. 354 (25): 2712-14. doi:10.1056/ ... Gollob MH, Jones DL, Krahn AD (2006). "Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation". New England ...
This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions (Ca2+) into the cell upon membrane polarization (see membrane potential and calcium in biology).[7] The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta and beta subunits in a 1:1:1 ratio. The S3-S4 linkers of Cav1.2 determine the gating phenotype and modulated gating kinetics of the channel.[8] Cav1.2 is widely expressed in the smooth muscle, pancreatic cells, fibroblasts, and neurons.[9][10] However, it is particularly important and well known for its expression in the heart where it mediates L-type currents, which causes calcium-induced calcium release from the ER Stores via ryanodine receptors. It depolarizes at -30mV and helps define the shape of the action potential in cardiac and smooth muscle.[8] The protein encoded by this gene ...
Two of the primary active constituents responsible for the antidepressant and anxiolytic benefits of Hypericum perforatum, also known as St. John's Wort, are hyperforin and adhyperforin.[9][10] These compounds are inhibitors of the reuptake of serotonin, norepinephrine, dopamine, γ-aminobutyric acid, and glutamate, and they are reported to exert these effects by binding to and activating TRPC6.[10][11] Recent results with hyperforin have cast doubt on these findings as similar currents are seen upon Hyperforin treatment regardless of the presence of TRPC6.[12] ...
The asymmetric structure consists of an N-terminal beta-trefoil domain and a C-terminal alpha helical domain with a folding pattern similar to an armadillo repeat fold. The split formed by the two terminals contains multiple arginine and lysine residues that coordinate the three phosphoryl groups of InsP3R.[2] The InsP3R complex is formed of four 313 kDa subunits. In amphibians, fish and mammals, there are 3 paralogs and these can form homo- or hetero-oligomers. InsP3R-1 is the most widely expressed of these three and is found in all tissue types and all developmental stages of life. It is additionally the means for further InsP3 receptor diversity in that it has as many as four splice sites with as many as 9 different optional exons or exon variants. Combinations of these can be introduced into a given transcript in order to modulate its pharmacological activity. ...
A channel that is "inwardly-rectifying" is one that passes current (positive charge) more easily in the inward direction (into the cell) than in the outward direction (out of the cell). It is thought that this current may play an important role in regulating neuronal activity, by helping to stabilize the resting membrane potential of the cell. By convention, inward current (positive charge moving into the cell) is displayed in voltage clamp as a downward deflection, while an outward current (positive charge moving out of the cell) is shown as an upward deflection. At membrane potentials negative to potassium's reversal potential, inwardly rectifying K+ channels support the flow of positively charged K+ ions into the cell, pushing the membrane potential back to the resting potential. This can be seen in figure 1: when the membrane potential is clamped negative to the channel's resting potential (e.g. -60 mV), inward current flows (i.e. positive charge flows into the cell). However, when the ...
The α1 subunit pore (~190 kDa in molecular mass) is the primary subunit necessary for channel functioning in the HVGCC, and consists of the characteristic four homologous I-IV domains containing six transmembrane α-helices each. The α1 subunit forms the Ca2+ selective pore, which contains voltage-sensing machinery and the drug/toxin-binding sites. A total of ten α1 subunits that have been identified in humans:[1] α1 subunit contains 4 homologous domains (labeled I-IV), each containing 6 transmembrane helices (S1-S6). This arrangement is analogous to a homo-tetramer formed by single-domain subunits of voltage-gated potassium channels (that also each contain 6 TM helices). The 4-domain architecture (and several key regulatory sites, such as the EF hand and IQ domain at the C-terminus) is also shared by the voltage gated sodium channels, which are thought to be evolutionary related to VGCCs.[8] The transmembrane helices from the 4 domains line up to form the channel proper; S5 and S6 helices ...
Voltage-dependent calcium channel gamma-4 subunit is a protein that in humans is encoded by the CACNG4 gene.[5][6] L-type calcium channels are composed of five subunits. The protein encoded by this gene represents one of these subunits, gamma, and is one of several gamma subunit proteins. It is an integral membrane protein that is thought to stabilize the calcium channel in an inactive (closed) state. This gene is a member of the neuronal calcium channel gamma subunit gene subfamily of the PMP-22/EMP/MP20 family and is located in a cluster with two similar gamma subunit-encoding genes.[6] ...
... is one of the seven mammalian TRPC (transient receptor potential canonical) proteins. TrpC5 is a multi-pass membrane protein and is thought to form a receptor-activated non-selective calcium permeant cation channel. The protein is active alone or as a heteromultimeric assembly with TRPC1, TRPC3, and TRPC4. It also interacts with multiple proteins including calmodulin, CABP1, enkurin, Na+-H+ exchange regulatory factor (NHERF), interferon-induced GTP-binding protein (MX1), ring finger protein 24 (RNF24), and SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).[5] TRPC4 and TRPC5 have been implicated in the mechanism of mercury toxicity[8] and neurological behavior.[9] ...
A Guide is a practical and valuable reference and text covering a wide scope of information about the connexin family of ... Connexins: A Guide is a practical and valuable reference and text covering a wide scope of information about the connexin ... Connexins in the Male Reproductive System Georges Pointis, C~line Fiorini, J~rome Gilleron, Diane Carette, Dominique Segretain ... Chemical Gating of Connexin Channels Rebecca Lewandowski, Junko Shibayama, Eva M. Oxford, Rosy Joshi-Mukherjee, Wanda Coombs, ...
The family of connexin (Cx) proteins is composed of 21 members in humans.... ... Connexins are proteins which assemble into channels that allow for small molecules to pass directly from one cell to another. ... The family of connexin (Cx) proteins is composed of 21 members in humans. All connexins (Cx32 and Cx26) share common features ... Cell Growth Control Connexin Expression Connexin Gene Congenital Hearing Loss Detrimental Side Effect These keywords were added ...
... "connexins." In this paper, we discuss current knowledge about connexins in diabetes. We also discuss mechanisms of connexin ... Connexins and Diabetes. Josephine A. Wright. ,1 Toby Richards. ,1 and David L. Becker1. 1Department of Vascular Surgery and ... G. Richard, "Connexin disorders of the skin," Clinics in Dermatology, vol. 23, no. 1, pp. 23-32, 2005. View at: Publisher Site ... Connexins are associated with the pathogenesis of both type I and type II diabetes (see Table 1) [12]. Cx36 forms the gap ...
Connexins are commonly named according to their molecular weights, e.g. Cx26 is the connexin protein of 26 kDa. A competing ... Media related to connexins at Wikimedia Commons Connexins at the US National Library of Medicine Medical Subject Headings (MeSH ... Kamasawa N, Sik A, Morita M, Yasumura T, Davidson KG, Nagy JI, Rash JE (2005). "Connexin-47 and connexin-32 in gap junctions of ... Aronica E, Gorter JA, Jansen GH, Leenstra S, Yankaya B, Troost D (May 2001). "Expression of connexin 43 and connexin 32 gap- ...
Connexin, N-terminal (IPR013092). Short name: Connexin_N Overlapping homologous superfamilies *Connexin, N-terminal domain ... Two sets of nomenclature have been used to identify the connexins. The first, and most commonly used, classifies the connexin ... Hydropathy analysis predicts that all cloned connexins share a common transmembrane (TM) topology. Each connexin is thought to ... The connexin protein family is encoded by at least 13 genes in rodents, with many homologues cloned from other species. They ...
Gating and regulation of connexin 43 (Cx43) hemichannels.. Contreras JE1, Sáez JC, Bukauskas FF, Bennett MV. ... Connexin 43 (Cx43) nonjunctional or "unapposed" hemichannels can open under physiological or pathological conditions. We ...
Rod pathways in the mammalian retina use connexin 36.. Mills SL1, OBrien JJ, Li W, OBrien J, Massey SC. ... These results place an identified neuronal connexin in the context of a well-defined retinal circuit. The absence of Cx36 in ... Here, we show that, in rabbit retina, an antibody to connexin 36 heavily labels processes of AII amacrine cells, a critical ... many other neurons known to be coupled suggests the presence of additional unidentified connexins in mammalian neurons. ...
Structural studies of N-terminal mutants of Connexin 26 and Connexin 32 using (1)H NMR spectroscopy.. Batir, Y., Bargiello, T.A ... The loss of this turn correlates with loss of Connexin 32 (Cx32) function by impaired trafficking to the cell membrane. Using ( ... Functional gap junctions are composed of connexin molecules with N-termini containing a flexible turn around G12, inserting the ... Functional gap junctions are composed of connexin molecules with N-termini containing a flexible turn around G12, inserting the ...
In this work, we discuss the current knowledge on connexin redox regulation and we propose the hypothesis that extracellular ... In this work, we discuss the current knowledge on connexin redox regulation and we propose the hypothesis that extracellular ... Connexin-based channels comprise hemichannels and gap junction channels. The opening of hemichannels allow for the flux of ions ... Connexin-based channels comprise hemichannels and gap junction channels. The opening of hemichannels allow for the flux of ions ...
Gap junctions are composed of connexins (Kumar and Gilula, 1996; Theis et al., 2005). Six connexins oligomerize to form a ... Connexin 43 Hemichannels Are Permeable to ATP. Jian Kang, Ning Kang, Ditte Lovatt, Arnulfo Torres, Zhuo Zhao, Jane Lin, Maiken ... Connexin 43 Hemichannels Are Permeable to ATP. Jian Kang, Ning Kang, Ditte Lovatt, Arnulfo Torres, Zhuo Zhao, Jane Lin, Maiken ... Connexin 43 Hemichannels Are Permeable to ATP. Jian Kang, Ning Kang, Ditte Lovatt, Arnulfo Torres, Zhuo Zhao, Jane Lin and ...
There are three isotypes of connexins expressed by the human myocardium, connexin-40 (Cx40), connexin-43 (Cx43), and connexin- ... Each connexon in turn is a hexamer of 6 connexin protein molecules. Connexin channels are selectively permeable to certain ions ... Within these gap junctions are present communication ports called connexins. Connexin channels are composed of two grummet ... Connexins: the Basis of Functional Coupling of Myocytes. Journal of Clinical and Basic Cardiology 2005; 8 (1-4): 19-22. PDF ...
Connexin the dots to prevent heart attacks with new BHF funding - University of Reading. Show access keys Access keys and ... Why Connexins?. Platelets are tiny blood cells that create clots by clumping together after an injury such as a cut. The ... Reading home> News and Events , Press Releases , Connexin the dots to prevent heart attacks with new British Heart Foundation ... The discovery that platelets use connexins to control this function means it could be an important target for efforts to reduce ...
Among the major connexins expressed in the vascular bed, connexin 40 (Cx40) is of particular interest as it is exclusively ... Spontaneous lung dysfunction and fibrosis in mice lacking connexin 40 and endothelial cell connexin 43. Am J Pathol. 2011;178(6 ... de Wit C. Connexins pave the way for vascular communication. News Physiol Sci. 2004;19:148-153.. View this article via: PubMed ... Connexin 43 mediates spread of Ca2+-dependent proinflammatory responses in lung capillaries. J Clin Invest. 2006;116(8):2193- ...
... with subsequent retrograde propagation to upstream arterioles via connexin 40 (Cx40) endothelial gap junctions. HPV was largely ...
Abcam provides specific protocols for Anti-Connexin 37 / GJA4 antibody (ab83788) : Western blot protocols, Immunohistochemistry ...
Buy our Recombinant Human Connexin 37 / GJA4 protein. Ab114495 is a full length protein produced in Wheat germ and has been ...
Connexins (Cxs) are a group of transmembrane proteins that assemble to form gap junction channels (GJCs). Each GJC is composed ... Connexins: Cellular Communication and Disease. Publicado en: Research UDD , 25 octubre 2018 ...
Connexin 36 (Cx36) is expressed extensively in the developing brain, with levels peaking at P14 after which its levels fall and ... Connexin 36 (Cx36) is expressed extensively in the developing brain, with levels peaking at P14 after which its levels fall and ... Undocked connexins, or hemichannels have also been identified and they provide a means to contact the extracellular environment ... 9. Prime G, Horn G, Sutor B (2000) Time-related changes in connexin mRNA abundance in the rat neocortex during postnatal ...
Suppression of connexin 43 phosphorylation promotes astrocyte survival and vascular regeneration in proliferative retinopathy. ... Astrocytes abundantly express connexin 43 (Cx43), a transmembrane protein that forms gap junction (GJ) channels and ... Suppression of connexin 43 phosphorylation promotes astrocyte survival and vascular regeneration in proliferative retinopathy ... Here we report that astrocytic connexin (Cx43) gap junction (GJ) channels are major contributors to astrocyte degeneration and ...
The focus of this review is to summarize current knowledge of the role of connexins and pannexins in platelet aggregation and ... In this respect, membrane channels formed by connexins and/or pannexins are of particular interest. While it is still not ... completely understood whether connexins function as hemichannels or gap junction channels to inhibit platelet aggregation, ... Pannexin- and Connexin-Mediated Intercellular Communication in Platelet Function. Filippo Molica 1,2,* , Florian B. Stierlin 1, ...
... connexin 43 include Encapsulation of Cardiomyocytes in a Fibrin Hydrogel for Cardiac Tissue Engineering , Visualizing and ...
Browse our Connexin 30.3/GJB4 Protein catalog backed by our Guarantee+. ... Connexin 30.3/GJB4 Proteins available through Novus Biologicals. ... We offer Connexin 30.3/GJB4 Peptides and Connexin 30.3/GJB4 ... Alternate Names for Connexin 30.3/GJB4 Proteins. Connexin 30.3/GJB4 protein, GJB4 protein, beta 4 protein, Connexin-30.3 ... Our Connexin 30.3/GJB4 Peptides and Connexin 30.3/GJB4 Proteins can be used in a variety of model species: Human. Use the list ...
... connexin-32 explanation free. What is connexin-32? Meaning of connexin-32 medical term. What does connexin-32 mean? ... Looking for online definition of connexin-32 in the Medical Dictionary? ... Connexin-32 , definition of connexin-32 by Medical dictionary https://medical-dictionary.thefreedictionary.com/connexin-32 ... redirected from connexin-32) GJB1. A gene on chromosome Xq13.1 that encodes a beta chain of the gap junction protein family or ...
... gene targeting of connexins in mice has provided new insights into connexin function and the significance of connexin diversity ... Genetic diseases and gene knockouts reveal diverse connexin functions Annu Rev Physiol. 1999;61:283-310. doi: 10.1146/annurev. ... Mutations in connexin genes underlie a variety of human diseases, including deafness, demyelinating neuropathies, and lens ... At the same time, new information on the physiological roles of vertebrate connexins has emerged from genetic studies. ...
... connexin-23 explanation free. What is connexin-23? Meaning of connexin-23 medical term. What does connexin-23 mean? ... Looking for online definition of connexin-23 in the Medical Dictionary? ... Connexin-23 , definition of connexin-23 by Medical dictionary https://medical-dictionary.thefreedictionary.com/connexin-23 ... redirected from connexin-23) GJE1. (1) A gene on chromosome 6q24.1 that encodes an epsilon chain of the gap junction protein ...
... Harissios ... Harissios Vliagoftis, Cory Ebeling, Ramses Ilarraza, et al., "Connexin 43 Expression on Peripheral Blood Eosinophils: Role of ...
Browse our Connexin 30/GJB6 product catalog backed by our Guarantee+. ... PTMs for Connexin 30/GJB6. Learn more about PTMs related to Connexin 30/GJB6.. Demethylation. Phosphorylation. Methylation. ... Diseases related to Connexin 30/GJB6. Discover more about diseases related to Connexin 30/GJB6.. Complete Hearing Loss. ... Connexins span the plasma membrane 4 times, with amino- and carboxy-terminal regions facing the cytoplasm. Connexin genes are ...
For these connexins, a variety of knock-outs, heart-specific knock-outs, conditional knock-outs, double knock-outs, knock-ins ... For these connexins, a variety of knock-outs, heart-specific knock-outs, conditional knock-outs, double knock-outs, knock-ins ... The connexin family of proteins consists of 24 members, varying in their biophysical properties and ability to combine with ... The connexin family of proteins consists of 24 members, varying in their biophysical properties and ability to combine with ...
Post-transcriptional regulation of connexins. Clàudia Salat-Canela, María José Muñoz, Marta Sesé, Santiago Ramón y Cajal, Trond ... Post-transcriptional regulation of connexins. Clàudia Salat-Canela, María José Muñoz, Marta Sesé, Santiago Ramón y Cajal, Trond ... Post-transcriptional regulation of connexins Message Subject (Your Name) has forwarded a page to you from Biochemical Society ... Abbreviations: ARE, adenylate/uridylate-rich element; Cx, connexin; eIF, eukaryotic initiation factor; HuR, Human antigen R ( ...
Connexin 30 indeed reduces laminin levels, inhibits the redistribution of the β1-integrin extracellular matrix receptors, and ... This study thus reveals that connexin 30 controls astroglial polarity during development.. We have also started to address the ... We recently found that connexin 30 (Cx30), an astroglial gap junction subunit expressed postnatally, tunes synaptic activity ... Wiring synaptic circuits with astroglial connexins: mechanisms, dynamics and impact for critical period plasticity. ...
  • The first, and most commonly used, classifies the connexin molecules according to molecular weight, such as connexin43 (abbreviated to Cx43), indicating a connexin of molecular weight close to 43kDa. (ebi.ac.uk)
  • Gating and regulation of connexin 43 (Cx43) hemichannels. (nih.gov)
  • Connexin 43 (Cx43) nonjunctional or "unapposed" hemichannels can open under physiological or pathological conditions. (nih.gov)
  • Previous studies have implicated connexin 43 (Cx43) in ATP release, but definitive proof that ATP exits through Cx43 hemichannels does not exist. (jneurosci.org)
  • There are three isotypes of connexins expressed by the human myocardium, connexin-40 (Cx40), connexin-43 (Cx43), and connexin-45 (Cx45). (kup.at)
  • Here we report that astrocytic connexin (Cx43) gap junction (GJ) channels are major contributors to astrocyte degeneration and vascular remodeling that follow tissue ischemia. (pnas.org)
  • Astrocytes abundantly express connexin 43 (Cx43), a transmembrane protein that forms gap junction (GJ) channels and hemichannels. (pnas.org)
  • This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. (mdpi.com)
  • Connexins are the proteins that constitute mammalian GJs, and Connexin43 (Cx43) is the most abundant isoform expressed in body cells. (bl.uk)
  • During folliculogenesis, developing oocytes are surrounded and nurtured by granulosa cells that are connected to one another by gap junctions containing the protein connexin 43 (Cx43). (biologists.org)
  • Upregulation of connexin 43 (Cx43) showed potential in enhancing immune surveillance that was suppressed in the tumor microenvironment. (medsci.org)
  • The impaired ability of antigen presentation of cancer cells can be restored by enhancement of gap-junction-forming molecule, connexin 43 (Cx43) [ 1 , 2 ]. (medsci.org)
  • Cx43, one of the wildly-studied connexin isoform, is considered to have correlation with immunity, disease formation and progression [ 4 , 5 ]. (medsci.org)
  • 23 This finding was explained as being the result of low levels of connexin expression and/or structural incompatibility between the extracellular loops E1 and E2 of Cx43 and Cx40. (ahajournals.org)
  • Objective: To observe the effect of angiotensin II (Ang II) on expression of gap junction channel protein connexin 43 (Cx43) in the proliferation process of vascular smooth muscle cells (VSMCs) during the early stage of arteriosclerosis. (ovid.com)
  • Atrial myocytes, for example, coexpress connexin (Cx) 40 and Cx43. (ahajournals.org)
  • In the present study, we show that cells coexpressing Cx40 and Cx43 are more susceptible to acidification-induced uncoupling than those cells expressing only one connexin isotype. (ahajournals.org)
  • The data show that the pKa (ie, the pH at which junctional conductance decreased to 50% from maximum) shifted from ≈6.7 when cells expressed only Cx40 or only Cx43 to ≈7.0 when one of the oocytes was coexpressing both connexins. (ahajournals.org)
  • The gene GJA1 encodes Connexin 43 (Cx43), which is the most expressed Connexin, and can be found in many human tissues including skin, bone, and brain. (biolegend.com)
  • We estimated the effects of TXL on I/R injury including neurological deficit assessment and cerebral infarct volume measurement via TTC staining, and detected the protein expression of Connexin 43 (Cx43) by western blot. (unboundmedicine.com)
  • Background: Connexin 43 (Cx43) is a member of the large family of gap junction proteins. (cellsignal.com)
  • Analysis of various connexin constructs in which the cytoplasmic carboxy tails were transposed, the cytoplasmic tail of Cx43 was truncated or a reporter protein, aequorin, was attached to the C-terminus showed that tail length was not the major determinant of the post-translational membrane insertion of connexins. (biochemj.org)
  • We have found that the restoration of density inhibition of human pancreatic cancer cells by the antiproliferative somatostatin receptor 2 (sst2) is due to overexpression of endogenous connexins Cx26 and Cx43 and consequent formation of functional gap junctions. (asm.org)
  • To determine whether downregulation of Connexin 43 (Cx43) expression promotes development of acellular capillaries (ACs), pericyte loss (PL), excess permeability, and retinal thickening in rat retinas. (molvis.org)
  • A recent study showed that gap junction protein connexin 43 (Cx43) and desmosome protein plakophilin-2 are working synergistically to modulate the BTB integrity by regulating the distribution of TJ-associated proteins at the Sertoli-Sertoli cell interface. (biomedsearch.com)
  • The aim of the study was to verify whether finasteride has a transgenerational effect on the expression of connexin 43 (Cx43), a gap junction protein in testes of the F1 generation. (termedia.pl)
  • We recently reported protein kinase A (PKA) to be part of a macromolecular signaling complex with ezrin and gap junction protein connexin 43 (Cx43) that provides cAMP-mediated control of gap junction communication. (biochemj.org)
  • The development of the vertebrate lens utilizes a sophisticated cell-cell communication network via gap junction channels, which are made up of at least three connexin isoforms, α8 (Cx50), α3 (Cx46) and α1 (Cx43), and which are encoded by three different genes. (biologists.org)
  • Connexin 43 (Cx43), also called Gjp1a, is the predominant protein located in intercellular plasma-membrane channels that directly connect the cytoplasm of adjacent Sertoli cells, between Sertoli cells and germ cells, and between Leydig cells [1]. (termedia.pl)
  • Method: To test this hypothesis we expressed connexin 43 (Cx43) in GJIC-deficient mammary epithelial tumor cells (HBL100) and examined their ability to form gap junctions, establish heterocellular GJIC and migrate through monolayers of human microvascular endothelial cells (HMVEC) grown on matrigel-coated coverslips. (uwo.ca)
  • The abnormalities in connexin-43 (Cx43) lead to conduction defects and contractile dysfunction. (surrey.ac.uk)
  • Both cell types express connexin 43 (Cx43) isoforms that permit the formation of GJs. (surrey.ac.uk)
  • The effects of T122 and T136 on GJ channels formed by several other connexins, including Cx26, Cx32, Cx40, Cx43, and Cx46 are illustrated in Figure 7B. (nih.gov)
  • This study evaluated whether n-3 polyunsaturated fatty acids (PUFAs) prevent vagally induced atrial fibrillation (AF) and affect atrial expression of connexins (CX40 and CX43 protein levels). (onlinejacc.org)
  • Should the Canine Connexin 43 (CX43) ELISA Kit is proven to show malperformance, you will receive a refund or a free replacement. (nrftd.org)
  • Description: A sandwich quantitative ELISA assay kit for detection of Canine Connexin 43 (CX43) in samples from tissue homogenates, cell lysates or other biological fluids. (nrftd.org)
  • Connexin 43 (Cx43) is the most abundant gap junction protein in bone and has been demonstrated as an integral component of skeletal homeostasis. (elsevier.com)
  • Here, we explored the mechanism of action of a connexin mimetic peptide by evaluating its effect on gap junction channels, connexin protein levels and hemichannel activity in fibroblast cells under normal conditions and following ischemia reperfusion injury which elevates Cx43 levels, increases hemichannel activity and causes cell death. (ntu.edu.sg)
  • DNAs coding for seven murine connexins (Cx) (Cx26, Cx31, Cx32, Cx37, Cx40, Cx43, and Cx45) are functionally expressed in human HeLa cells that were deficient in gap junctional communication. (rupress.org)
  • Among alpha-type connexins, Cx40 does not communicate with Cx43. (rupress.org)
  • Adjacent astrocytes can make direct communication through gap junctions formed by connexin 43 (Cx43) in the central nervous system. (elsevier.com)
  • Since Cx43 is the connexin isoform expressed preferentially in astrocytes in the spinal cord, we used a small interfering RNA (siRNA) approach to examine whether suppression of spinal Cx43 expression inhibits mechanical hypersensitivity in rats after an L5 spinal nerve ligation (SNL). (elsevier.com)
  • Connexins: A Guide is a practical and valuable reference and text covering a wide scope of information about the connexin family of membrane channel proteins. (springer.com)
  • it is a comprehensive and comprehensible narrative of the uncommonly diverse connexin field, making previously hard-to-find information easily accessible, while also presenting intelligible insights into the extensive experimental methods and conceptual frameworks necessary to appreciate and understand the important roles that connexin channel proteins play in health and disease. (springer.com)
  • Connexins are proteins which assemble into channels that allow for small molecules to pass directly from one cell to another. (springer.com)
  • The family of connexin (Cx) proteins is composed of 21 members in humans. (springer.com)
  • Gap junctions are highly specialized transmembrane structures that are formed by connexon hemichannels, which are further assembled from proteins called "connexins. (hindawi.com)
  • In vertebrates, gap junction channels are assembled of trans-membrane proteins called "connexins. (hindawi.com)
  • The connexins are a family of integral membrane proteins that oligomerise to form intercellular channels that are clustered at gap junctions. (ebi.ac.uk)
  • Connexins (Cx) (TC# 1.A.24), or gap junction proteins, are structurally related transmembrane proteins that assemble to form vertebrate gap junctions. (wikipedia.org)
  • Following a vote at the Gap Junction Conference (2007) in Elsinore the community agreed to use the GJ nomenclature system for the genes that encode connexins, but wished to retain the connexin nomenclature for the encoded proteins using the weight of the human protein for the numbering of orthologous proteins. (wikipedia.org)
  • Connexin gap junctions are found only in vertebrates, while a functionally analogous (but genetically unrelated) group of proteins, the innexins, are responsible for gap junctions in invertebrate species. (wikipedia.org)
  • Connexins are a large family of transmembrane proteins involved in cellular communication. (frontiersin.org)
  • Professor Jonathan Gibbins has been awarded £246,000 by the British Heart Foundation (BHF) to study a group of proteins called connexins that are believed to play a crucial role in clot formation. (reading.ac.uk)
  • To strengthen their ability to bind together, platelets communicate with each other through proteins called connexins. (reading.ac.uk)
  • Connexins (Cxs) are a group of transmembrane proteins that assemble to form gap junction channels (GJCs). (udd.cl)
  • We offer Connexin 30.3/GJB4 Peptides and Connexin 30.3/GJB4 Proteins for use in common research applications: ELISA, Protein Array, Western Blot. (novusbio.com)
  • Our Connexin 30.3/GJB4 Peptides and Connexin 30.3/GJB4 Proteins can be used in a variety of model species: Human. (novusbio.com)
  • Choose from our Connexin 30.3/GJB4 Peptides and Proteins. (novusbio.com)
  • The connexin family of proteins consists of more than 20 members varying in their biophysical properties and ability to combine with other connexins into heteromeric gap junction channels. (frontiersin.org)
  • Each connexon consists of 6 connexin subunits, and a homomeric gap junction channel consists of 12 Cx proteins of the same isoform. (frontiersin.org)
  • Their structural subunits are four-transmembrane proteins named connexins (Cxs), which can be post-transcriptionally regulated by developmental and cellular signalling cues. (biochemsoctrans.org)
  • GJBs (gap-junction proteins or connexins) play crucial functional roles associated with these channels. (thermofisher.com)
  • They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. (mdpi.com)
  • Each gap junction channel is made by docking of two hemichannels or connexons, each formed by assembly of six proteins (connexins). (eurekaselect.com)
  • Some studies have revealed that connexins could have gap junction intercellular communication (GJIC) independent roles by interacting with diverse proteins (reviewed in Herve et al. (usc.edu)
  • Gap junctional intercellular communication is a mechanism for direct cell-to-cell signaling and is mediated by gap junctions, which consist of transmembrane proteins called connexins. (eurekaselect.com)
  • The liver was among the first organs in which connexin proteins have been identified. (ugent.be)
  • Connexin family proteins assemble into hexameric channels called hemichannels/connexons, which function as transmembrane channels or dock together to form gap junction intercellular channels (GJIChs). (sciencemag.org)
  • In vertebrates, various connexin family proteins assemble into hexameric channels called hemichannels/connexons in cell membrane, and two hemichannels from adjacent cells dock together to form a gap junction intercellular channel (GJICh) ( 1 - 3 ). (sciencemag.org)
  • The connexin family of proteins forms hexameric complexes called connexons that facilitate movement of low molecular weight proteins between cells via gap junctions. (biotium.com)
  • Connexin proteins share a common topology of four transmembrane alphalpha-helicaldomains, two extracellular loops, a cytoplasmic loop and cytoplasmic N- and C-termini. (biotium.com)
  • Connexins are a family of transmembrane proteins that assemble to form vertebrate gap junctions, thus also called Gap Junction Proteins. (biolegend.com)
  • This gene encodes a member of the connexin family of proteins, which form channels in the membranes that surround cells. (elifesciences.org)
  • Connexins (Cxs) are transmembrane proteins that form channels which allow direct intercellular communication (IC) between neighbouring cells via gap junctions. (biochemsoctrans.org)
  • The structural proteins comprising these channels, collectively called connexins, are members of a highly related multigene family consisting of at least 13 members. (hku.hk)
  • Connexins (Cxs) are integral membrane proteins of vertebrates that associate to form hexameric transmembrane channels, named hemichannels. (bio-protocol.org)
  • Tumor cell attachment to pulmonary vasculature, tumor growth, and connexin-43 expression was studied in metastatic lung tumor sections obtained after tail-vein injection into nude mice of syngeneic breast cancer cell lines, overexpressing wild type connexin-43 or dominant-negatively mutated connexin-43 proteins. (biomedcentral.com)
  • Currently, only serial thin-section transmission electron microscopy and freeze-fracture replica immunogold labeling have sufficient resolution to assign connexin proteins to either or both sides of gap junction plaques. (deepdyve.com)
  • The paucity of specific pharmacological agents has been a major impediment for delineating the roles of gap junction (GJ) channels formed by connexin proteins in physiology and pathophysiology. (nih.gov)
  • Results indicate that previously reported regulation of connexin 43 and COX-2 proteins during equine COC maturation may involve post-transcriptional mechanisms. (biomedcentral.com)
  • The process of cumulus expansion is accompanied by modifications of gap junctions, which contain transmembrane channels formed by hexamers of proteins belonging to the connexin family. (biomedcentral.com)
  • Changes in the expression of gap junction proteins (connexins) in hamster tongue epithelium during wound healing and carcinogenesis. (oup.com)
  • We examined changes in the expression and localization of connexin proteins and transcripts by means of immunofluorescence and in situ hybridization in normal conditions, wound healing and carcinogenesis using hamster tongue epithelium, in which differentiation, migration and growth of keratinocytes takes place physiologically and pathologically. (oup.com)
  • During wound healing, the expression and localization of connexin proteins and transcripts were changed drastically. (oup.com)
  • Cx26 is the connexin protein of 26 kDa. (wikipedia.org)
  • However, some connexins, such as Cx26 may be transported independent of the Golgi. (wikipedia.org)
  • PCR and immunohistochemical analysis identified the presence of connexins (Cx26/Cx32/Cx36) in the human fetal cortex. (sigmaaldrich.com)
  • Velocity sedimentation on sucrose gradients showed that a small proportion of connexin (Cx) 26 and Cx32 that were co-translationally translocated into microsomes were oligomers of Cx26 and Cx32. (biochemj.org)
  • The connexin 26 (Cx26) ( GJB2) gene is of particular interest to study in relation to noise, since the gene encodes the gap junction protein Cx26. (diva-portal.org)
  • Two other beta-type connexin transfectants, HeLa-Cx26 and -Cx32, do not transmit Lucifer yellow to any of the alpha-type connexins analyzed. (rupress.org)
  • The connexin protein family is encoded by at least 13 genes in rodents, with many homologues cloned from other species. (ebi.ac.uk)
  • To circumvent this problem, particular connexin-encoding genes have been subjected to targeted-disruption in mice, and the phenotype of the resulting animals investigated. (ebi.ac.uk)
  • Further insight into the functional roles of connexins has come from the discovery that a number of human diseases are caused by mutations in connexin genes. (ebi.ac.uk)
  • For this reason, mutations in connexin-encoding genes can lead to functional and developmental abnormalities. (wikipedia.org)
  • In humans, there are 21 genes encoding for connexins ( Söhl and Willecke, 2003 ). (frontiersin.org)
  • Mutations in connexin genes underlie a variety of human diseases, including deafness, demyelinating neuropathies, and lens cataracts. (nih.gov)
  • Connexin genes are expressed in a cell type-specific manner with overlapping specificity. (novusbio.com)
  • Discover related pathways, diseases and genes to Connexin 30/GJB6. (novusbio.com)
  • Mutational alterations in the connexin genes are associated with the occurrence of multiple pathologies, such as peripheral neuropathies, cardiovascular diseases, dermatological diseases, hereditary deafness and cataract. (eurekaselect.com)
  • Involvement of aberrant gap junctional intercellular communication in carcinogenesis and tumor suppressing role of connexin genes has been well documented. (eurekaselect.com)
  • Twenty human connexin genes, except the highly diversified connexin 23 (Cx23)/GJE1 member, share 55 to 82% amino acid sequence similarity in the regions spanning the N-terminal helix (NTH), four transmembrane helices (TM helices), and two extracellular loops (ECLs) (fig. S1). (sciencemag.org)
  • Finally, mutations in two connexin genes have been linked to human diseases. (hku.hk)
  • and this suggests that different regulatory machinery may control the expression of α3 and α8 connexin genes in lens epithelial cells, despite the fact that the same factors may control their expression in fiber cells. (biologists.org)
  • Here, we show that, in rabbit retina, an antibody to connexin 36 heavily labels processes of AII amacrine cells, a critical interneuron in the rod pathway. (nih.gov)
  • The following antibody was used in this experiment: Connexin 36 Polyclonal Antibody from Thermo Fisher Scientific, catalog # 51-6200, RRID AB_2533912. (thermofisher.com)
  • The following antibody was used in this experiment: Connexin 26 Polyclonal Antibody from Thermo Fisher Scientific, catalog # 71-0500, RRID AB_2533971. (thermofisher.com)
  • Due to sequence homologies, this antibody is also expected to react with canine (100% homology) and mouse (92% homology) Connexin 45. (bio-medicine.org)
  • Connexin 43/GJA1 Monoclonal antibody specifically detects Connexin 43/GJA1 in Human samples. (fishersci.com)
  • This peptide was used for the production of goat polyclonal anti-Connexin 50 / GJA8 antibody (GTX88154). (genetex.com)
  • This antibody is specific for GJB2 / Connexin 26. (genetex.com)
  • This antibody recognizes a protein of 27-32 kDa, identified as Connexin 32. (biotium.com)
  • Catalog number key for antibody number 1641, Anti-Connexin-32 (R5.21C) The prefix indicates conjugation, followed by the antibody number and size suffix. (biotium.com)
  • Western blot of Biotin anti-Connexin 43, 360-382 antibody (clone P2C4). (biolegend.com)
  • IHC staining of Biotin anti-Connexin 43, 360-382 antibody (clone P2C4) on formalin-fixed paraffin-embedded mouse brain tissue. (biolegend.com)
  • IHC staining of Biotin anti-Connexin 43, 360-382 antibody (clone P2C4) on formalin-fixed paraffin-embedded human brain tissue. (biolegend.com)
  • Connexin 40 antibody LS-C14547 is an unconjugated rabbit polyclonal antibody to Connexin 40 (GJA5 / CX40) (C-Terminus) from mouse. (lsbio.com)
  • High-resolution immunofluorescence microscopy and Western blot analysis was performed using a connexin-43 monoclonal antibody. (biomedcentral.com)
  • The connexin gene family is diverse, with twenty-one identified members in the sequenced human genome, and twenty in the mouse (nineteen of which are orthologous pairs). (wikipedia.org)
  • In addition, gene targeting of connexins in mice has provided new insights into connexin function and the significance of connexin diversity. (nih.gov)
  • 1) A gene on chromosome 6q24.1 that encodes an epsilon chain of the gap junction protein family or connexins. (thefreedictionary.com)
  • The connexin gene family codes for the protein subunits of gap junction channels that mediate direct diffusion of ions and metabolites between the cytoplasm of adjacent cells. (novusbio.com)
  • Connexin 26 is a protein establish on the GJB2 gene which mostly relates as the cause of congenital hearing loss . (biology-online.org)
  • The mutation of connexin 26 gene modulates the harshness of hearing loss due to 1555A-G mitochondrial mutation as a consequence it is accountable for at least 20% of genetic hearing loss and 10% childhood hearing loss though in ethnic populations more than 80% cases of non-syndromic recessive deafness caused by the mutation of these gene . (biology-online.org)
  • GJA9, also called connexin-36 (CX36), is a member of the connexin gene family that is expressed predominantly in mammalian neurons. (thermofisher.com)
  • To determine the specific role of alpha3 connexin in vivo, the alpha3 connexin gene was disrupted in mice. (nih.gov)
  • Although the absence of alpha3 connexin had no obvious influence on the early stages of lens formation and the differentiation of lens fibers, mice homozygous for the disrupted alpha3 gene developed nuclear cataracts that were associated with the proteolysis of crystallins. (nih.gov)
  • 21 members of the connexin gene family are likely to be expressed in the human genome. (eurekaselect.com)
  • A technique called a genetic screen revealed that the same patterning defects are also seen in the body of zebrafish with mutations to another gene called luchs , which encodes a different connexin protein to the one produced by leo . (elifesciences.org)
  • The staining of the knock-in lacZ reporter gene showed the promoter activity of α8 connexin is much higher than that of α3 connexin in embryonic lenses and in adult lens epithelium. (biologists.org)
  • Is the connexin 26 gene (causes deafness) passed down from generations? (healthtap.com)
  • Tang J, Li L, Hu LQ, Cai QY, Chen L. Association between 1019C/T polymorphism in the connexin 37 gene and dilated cardiomyopathy. (minervamedica.it)
  • Here, we suppressed the Connexin 43 (Cx 43) gene expression during in vitro development of ovine pre-implantation embryos using the RNAi method. (koreascience.or.kr)
  • The hemichannel is made of six connexin subunits, each of which consist of four transmembrane segments. (wikipedia.org)
  • Oligomerization of six connexin subunits forms a channel known as hemichannel. (frontiersin.org)
  • Six connexins oligomerize to form a hemichannel (connexon), which docks with a hemichannel in a neighboring cell to form a gap-junction channel. (jneurosci.org)
  • Under injury and disease conditions gap junction coupling may be reduced, but both Connexin 43 expression and hemichannel opening are increased. (arvojournals.org)
  • In the bright light retinal injury model intravitreal injection of connexin hemichannel blocking peptides reduces inflammation and significantly improves functional outcomes (electroretinograms). (arvojournals.org)
  • 12 16 17 18 19 20 However, not every homomeric hemichannel will form a functional gap junction channel with another homomeric hemichannel derived from a different connexin. (ahajournals.org)
  • Compared with available structures of GJICh in open conformation, Cx31.3 hemichannel shows substantial structural changes of highly conserved regions in the connexin family, including opening of calcium ion-binding tunnels, reorganization of salt-bridge networks, exposure of lipid-binding sites, and collocation of amino-terminal helices at the cytoplasmic entrance. (sciencemag.org)
  • 2 3 4 5 Recent evidence strongly suggests that these two connexins oligomerize within the same hemichannel, forming a heteromeric connexon. (ahajournals.org)
  • Connexins assemble as a hexamer and are transported to the plasma membrane to create a hemichannel that can associate with hemichannels on nearby cells to create cell-to-cell channels. (cellsignal.com)
  • To form a gap junction channel, each cell of an adjacent pair synthesizes a hemichannel composed of six connexin subunits called a connexon. (asm.org)
  • Although the regulation of connexins in GJs has been well characterized, the molecular determinants controlling connexin-hemichannel activity are unresolved. (ugent.be)
  • Possible communication diversity is increased further by the fact that gap junctions may be formed by the association of different connexin isoforms from apposing cells. (ebi.ac.uk)
  • Due to their ubiquity and overlapping tissue distributions, it has proved difficult to elucidate the functions of individual connexin isoforms. (ebi.ac.uk)
  • Around half the connexin isoforms have been investigated in this manner [ PMID: 9861669 ]. (ebi.ac.uk)
  • During development, two connexin isoforms, connexin36 (Cx36) and Cx45, are expressed in bipolar cells and RGCs, and therefore provide a potential substrate for coordinating network activity. (jneurosci.org)
  • Here, I investigated the expression patterns of 12 connexin isoforms according to the sequences published on chicken nucleotide database on the NCBI website. (usc.edu)
  • Connexins belong to a large family of at least 20 protein isoforms in humans whose expression is tissue specific ( 48 , 60 ). (asm.org)
  • Gap junction channels are formed when connexin (Cx) subunits situated in adjacent plasma membranes dock together. (plos.org)
  • Cardiac conduction is mediated by gap junction channels that are formed by connexin (Cx) protein subunits. (frontiersin.org)
  • Gap junction channels consist of connexin (Cx) protein subunits. (frontiersin.org)
  • Gap junction channels consist of connexin protein subunits, which are encoded by a multigene family. (thermofisher.com)
  • Cxs (connexins), the protein subunits forming gap junction intercellular communication channels, are transported to the plasma membrane after oligomerizing into hexameric assemblies called connexin hemichannels (CxHcs) or connexons, which dock head-to-head with partner hexameric channels positioned on neighbouring cells. (portlandpress.com)
  • Intercellular gap junction channels, formed by at least three different connexin protein subunits, α1 (connexin43 or Gja1), α3 (connexin46 or Gja3) and α8 (connexin50 or Gja8), are utilized to transport metabolites, ions and water in the lens. (deepdyve.com)
  • In combination with physiological and biochemical analyses, recent genetic studies have significantly improved our understanding about the roles of diverse gap junction channels formed by α3 and α8 connexin subunits during lens development and cataract formation. (deepdyve.com)
  • The loss of this turn correlates with loss of Connexin 32 (Cx32) function by impaired trafficking to the cell membrane. (rcsb.org)
  • On the other hand, propidium iodide and ethidium bromide penetrate very poorly or not at all through Cx31 and Cx32 channels, respectively, but pass through channels of other connexins. (rupress.org)
  • Recognizes Human Connexin 45. (bio-medicine.org)
  • Detects human Connexin 43/GJA1. (fishersci.com)
  • Stains human Connexin 43/GJA1 transfectants but not irrelevant transfectants in flow cytometry. (fishersci.com)
  • We determined the cryo-electron microscopy structures of human connexin 31.3 (Cx31.3)/GJC3 hemichannels in the presence and absence of calcium ions and with a hearing-loss mutation R15G at 2.3-, 2.5-, and 2.6-Å resolutions, respectively. (sciencemag.org)
  • Here we speculated that the ideal site for oxygen sensing might instead be at the alveolocapillary level, with subsequent retrograde propagation to upstream arterioles via connexin 40 (Cx40) endothelial gap junctions. (jci.org)
  • This peptide corresponds to the GAP27 domain of the second extracellular loop of dominant vascular connexin (Cx40), designated as 40Gap 27. (mobitec.com)
  • Intercellular communication between cells is realized through gap junction channels formed by connexins (Cx). (springer.com)
  • Gap junctional intercellular communication (GJIC) and connexin (Cx) expression were reported in association with carcinogenesis in various types of tumours. (spandidos-publications.com)
  • Consistently, the lack of growth control and the inability to differentiate or apoptose in most cancer cells are related to altered connexin expression and consequent dysfunctional gap junction intercellular communication. (asm.org)
  • Within this functional unit, connexin (Cx) channels are of utmost importance for intercellular communication between the different cellular compartments. (ugent.be)
  • Connexin-assembled gap junctions (GJs) and hemichannels coordinate intercellular signaling processes. (ugent.be)
  • Since the cloning of the first connexin in 1986, considerable progress has been made in our understanding of the complex molecular switches that control the formation and permeability of intercellular channels. (hku.hk)
  • The development of more specific approaches (dominant negative mutants, knockouts, transgenes) to study the functional role of connexins in organ homeostasis is providing a new perception about the significance of connexin diversity and the regulation of intercellular communication. (hku.hk)
  • Chondrocytes extracted from adult arti cular cartilage and grown in primary culture express connexin 43 and form functional gap junctions capable of sustaining the propagation of intercellular Ca2+ waves. (iospress.com)
  • The various connexins have been observed to combine into both homomeric and heteromeric gap junctions, each of which may exhibit different functional properties including pore conductance, size selectivity, charge selectivity, voltage gating, and chemical gating. (wikipedia.org)
  • Functional gap junctions are composed of connexin molecules with N-termini containing a flexible turn around G12, inserting the N-termini into the channel pore allowing voltage gating. (rcsb.org)
  • The biogenesis of connexins and their assembly into functional gap junction hemichannels (connexons) was studied with the use of a cell-free transcription/translation system. (biochemj.org)
  • Thus, connexins differ in their ability to form functional heterotypic gap junctions among mammalian cells. (rupress.org)
  • Two connexons then interact (likely via the extracellular loops of their connexins) to form the complete gap junction channel. (ebi.ac.uk)
  • Each gap junction is composed of two hemichannels, or connexons, which consist of homo- or heterohexameric arrays of connexins, and the connexon in one plasma membrane docks end-to-end with a connexon in the membrane of a closely opposed cell. (wikipedia.org)
  • Connexins are assembled in groups of six to form hemichannels, or connexons, and two hemichannels then combine to form a gap junction. (wikipedia.org)
  • Connexin channels are composed of two grummet shaped hemi-channels called connexons. (kup.at)
  • When two homomeric connexons consisting of different connexins are apposed, a heterotypic channel may form if those connexins are compatible. (frontiersin.org)
  • Connexins associate in groups of 6 and are organized radially around a central pore to form connexons. (thermofisher.com)
  • In mammals, paracrine signaling is in part mediated by single membrane channels formed by connexins (connexons/hemichannels) or pannexins (pannexons), which are two different membrane protein families composed of about 20 and 3 members, respectively. (frontiersin.org)
  • Consisting two connexons and each composed of six connexins, gap junction is responsible for cell-cell molecule transferring and homeostasis maintenance [ 3 ]. (medsci.org)
  • Contiguous connexins (Cxs) may form homomeric or heteromeric gap junction hemichannels (connexons) on the cell membrane ( 1 ). (spandidos-publications.com)
  • However, in vitro studies have shown that not all possible combinations of connexins produce active channels [ PMID: 8811187 , PMID: 8608591 ]. (ebi.ac.uk)
  • Connexin-based channels comprise hemichannels and gap junction channels. (frontiersin.org)
  • Connexin channels are selectively permeable to certain ions and molecules less than 1kDa in weight and less than 2nm in diameter. (kup.at)
  • In this respect, membrane channels formed by connexins and/or pannexins are of particular interest. (mdpi.com)
  • While it is still not completely understood whether connexins function as hemichannels or gap junction channels to inhibit platelet aggregation, there is clear-cut evidence for a specific implication of pannexin1 channels in collagen-induced aggregation. (mdpi.com)
  • The gap junction channels have unique properties depending on the type of connexins constituting the channel. (novusbio.com)
  • Gap junction channels formed by alpha3 (Cx46) and alpha8 (Cx50) connexin provide pathways for communication between the fiber cells in the normal transparent lens. (nih.gov)
  • Homotypic gap junction channels are defined to consist of two identical hemichannels made from one type of connexin. (ahajournals.org)
  • Heteromeric channels are defined to consist of two hemichannels composed of more than one type of connexin. (ahajournals.org)
  • 16 Heterotypic channels consist of two different hemichannels, each of which is made of a different type of connexin. (ahajournals.org)
  • Communication among cells via direct cell-cell contact by connexin gap junctions, or between cell and extracellular environment via pannexin channels or connexin hemichannels, is a key factor in cell function and tissue homeostasis. (springer.com)
  • Upon malignant transformation in different cancer types, the dysregulation of these connexin and pannexin channels and their effect in cellular communication, can either enhance or suppress tumorigenesis and metastasis. (springer.com)
  • In the current review, we will highlight the most recent literature on the role of connexins in cancer, and introduce the more recently discovered pannexin channels and their proposed function in different cancer types. (springer.com)
  • The current paper provides a concise overview of the features of connexins, pannexins and their channels in the liver. (ugent.be)
  • 2014). Connexin and pannexin (hemi)channels in the liver. (ugent.be)
  • heteromeric' gap junctions are made from two different half channels, each consisting of a different connexin protein. (elifesciences.org)
  • Connexin channels at the glio-vascula. (ugent.be)
  • Connexins are best known as the building blocks of gap junction (GJ) channels that enable direct cell-cell transfer of metabolic, biochemical and electric signals. (ugent.be)
  • De Bock M, Leybaert L, Giaume C. Connexin channels at the glio-vascular interface : gatekeepers of the brain. (ugent.be)
  • Fontes JD, Ramsey J, Polk JM, Koop A, Denisova JV, Belousov AB (2015) Death of Neurons following Injury Requires Conductive Neuronal Gap Junction Channels but Not a Specific Connexin. (ku.edu)
  • Spatial separation of endothelial small- and intermediate-conductance calcium-activated potassium channels (K(Ca)) and connexins: possible relationship to vasodilator function? (semanticscholar.org)
  • Here, we used the selective optimization of side activities (SOSA) approach, which has led to the design of high affinity inhibitors of other ion channels, to identify a specific inhibitor for channels formed by Cx50, a connexin subtype that is primarily expressed in the lens. (nih.gov)
  • Both compounds exhibit at least 10-fold selectivity over other connexins as well as major neuronal and cardiac voltage-gated K(+) and Na(+) channels. (nih.gov)
  • Both compounds exhibited high selectivity for Cx50 channels over other connexin subtypes. (nih.gov)
  • These results demonstrate that inhibition of Cx50 GJ channels by T122 and T136 is highly connexin-selective. (nih.gov)
  • Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells. (rupress.org)
  • Our results show that Lucifer yellow can pass through all connexin channels analyzed. (rupress.org)
  • Permeability through different connexin channels appears to be dependent on the molecular structure of each tracer, i.e. size, charge and possibly rigidity. (rupress.org)
  • This supports the hypothesis that different connexin channels show different permeabilities to second messenger molecules as well as metabolites and may fulfill in this way their specific role in growth control and differentiation of cell types. (rupress.org)
  • Future research could be directed at achieving ways of optimising and modulating connexin expression as a therapeutic tool. (kup.at)
  • Abstract -Gap junctions are formed by oligomerization of a protein called connexin. (ahajournals.org)
  • Invertebrates utilise a different family of molecules, innexins, that share a similar predicted secondary structure to the vertebrate connexins, but have no sequence identity to them [ PMID: 9769729 ]. (ebi.ac.uk)
  • It is also in the ER that the oligomerization of connexin molecules into hemichannels begins, a process which may continue in the UR-Golgi intermediate compartment as well. (wikipedia.org)
  • Each connexon in turn is a hexamer of 6 connexin protein molecules. (kup.at)
  • Thus, connexin hemichannels and pannexons permit the release of significant quantities of autocrine/paracrine signaling molecules (e.g. (frontiersin.org)
  • Gap junctions are formed by the direct docking of two hexamers of connexins (Cxs) which allow the exchange of cellular contents, such as ions, second messengers and small molecules, between neighboring cells. (usc.edu)
  • Connexins are, for the most part, highly regulatable molecules. (ahajournals.org)
  • Pulse-chase with first FlAsH and then ReAsH revealed newer (i.e., red) molecules of connexin at the outer edge of large clusters of gap junctions known as plaques. (rupress.org)
  • Green molecules were concentrated in the center, indicating that older connexins are endocytosed from the middle of the plaques. (rupress.org)
  • We compare the permeabilities of gap junctions comprised of different connexins to iontophoretically injected tracer molecules. (rupress.org)
  • The absence of Cx36 in many other neurons known to be coupled suggests the presence of additional unidentified connexins in mammalian neurons. (nih.gov)
  • Connexin 36 ( Cx36) is expressed extensively in the developing brain, with levels peaking at P14 after which its levels fall and its expression becomes entirely neuronal. (plos.org)
  • Peptide corresponding to a sequence located in the cytoplasmic loop between the second and third transmembrane domains of rat and mouse Connexin 36 (Cx36). (thermofisher.com)
  • Pharmacological blockade or genetic knockout of neuronal connexin 36 (Cx36)-containing gap junctions reduces neuronal death caused by ischemia, traumatic brain injury and NMDA receptor (NMDAR)-mediated excitotoxicity. (ku.edu)
  • Individual transmembrane connexins (coloured blue and orange) assemble into hexamers called "connexon hemichannels. (hindawi.com)
  • Six connexins are thought to associate to form a hemi-channel, or connexon. (ebi.ac.uk)
  • Pannexins or Connexins? (springer.com)
  • The focus of this review is to summarize current knowledge of the role of connexins and pannexins in platelet aggregation and to discuss possible pharmacological approaches along with their limitations and future perspectives for new potential therapies. (mdpi.com)
  • Analysis of the mechanisms of channel assembly has revealed the selectivity of inter-connexin interactions and uncovered novel characteristics of the channel permeability and gating behavior. (hku.hk)
  • It is in the ER that connexins are properly folded, yielding two extracellular loops, EL-1 and EL-2. (wikipedia.org)
  • Some of these peptides enhance communication while others interfere with connexin binding partners or bind to the intracellular and extracellular loops of connexins. (ntu.edu.sg)
  • Structure/function studies have begun to provide a molecular understanding of the significance of connexin diversity and demonstrated the unique regulation of connexins by tyrosine kinases and oncogenes. (hku.hk)
  • Each Connexin 30.3/GJB4 Peptide and Connexin 30.3/GJB4 Protein is fully covered by our Guarantee+, to give you complete peace of mind and the support when you need it. (novusbio.com)
  • Peptide corresponding to a portion of the cytoplasmic loop of rat connexin 26. (thermofisher.com)
  • KLH-conjugated peptide corresponding to amino acids 360-382 of Connexin 43. (biolegend.com)
  • Busby M, Hallett MT, Plante I. The Complex Subtype-Dependent Role of Connexin 43 ( GJA1 ) in Breast Cancer. (mdpi.com)
  • Conditional Lyz2 cre/cre Gja1 flox/flox mice were developed to specifically assess Connexin-43 impact in macrophages. (elifesciences.org)
  • Here, we report the effects of constitutive activation of α 1 -adrenergic signaling on connexin phosphorylation and cardiac conduction. (ahajournals.org)
  • Changes in connexin phosphorylation can also alter gap-junction conductance in vitro. (ahajournals.org)
  • 12-14 Connexin phosphorylation depends on the balance between protein kinases and protein phosphatases. (ahajournals.org)
  • The loss of connexin function in cancer cells or in cells treated with tumor promoters results from various defects, including alteration of transcription ( 51 , 62 ), protein trafficking ( 16 , 47 ), stability ( 26 , 45 ), or phosphorylation ( 36 , 52 ). (asm.org)
  • Incidence of protein on actin bridges between endothelium and smooth muscle in arterioles demonstrates heterogeneous connexin expression and phosphorylation. (semanticscholar.org)
  • Rod pathways in the mammalian retina use connexin 36. (nih.gov)
  • The mammalian heart shows regional differences both in connexin expression profile and in degree of electrical coupling. (frontiersin.org)
  • We recently found that connexin 30 (Cx30), an astroglial gap junction subunit expressed postnatally, tunes synaptic activity via an unprecedented non-channel function setting the proximity of glial processes to synaptic clefts, essential for synaptic glutamate clearance efficacy. (europa.eu)
  • The gap junction protein Cx30 was found to be an unusually stable, long-lived connexin, which might underlie its specific role in the epidermis and cochlea. (biologists.org)
  • Here, we demonstrate that a fraction of brain pericytes express Connexin 30 (Cx30), a gap junction protein, which, in the brain parenchyma, was thought to be exclusively found in astrocytes. (springer.com)
  • Normal differentiated and contact-inhibited cells express at least one connexin isoform that assembles, alone or in combination, into gap junctions. (asm.org)
  • suggest that heteromeric gap junctions formed from the connexins produced by leo and luchs are important for xanthophores and melanophores to communicate with each other and so form the stripy patterning seen on the body of the zebrafish. (elifesciences.org)
  • Consistently, connexin expression is impaired in most cancer cells, and forced expression of connexins following cDNA transfection reverses the tumor phenotype. (asm.org)
  • The alteration of connexin expression is of importance, as their forced expression, following cDNA transfection, can promote cell density inhibition and reverse the tumor phenotype ( 34 ). (asm.org)
  • We hypothesized that, in this multi-stage scheme, connexin-43 is centrally involved as a cell adhesion molecule mediating metastatic tumor attachment to the pulmonary endothelium. (biomedcentral.com)
  • Upregulation of connexin-43 was observed in tumor cell-endothelial cell contact areas in vitro and in vivo , and in areas of intratumor blood vessels and in micrometastatic foci. (biomedcentral.com)
  • The marked upregulation of connexin-43 in tumor cell-endothelial cell contact areas, whether in preexisting 'homing' vessels or in newly formed tumor vessels, suggests that connexin-43 can serve as a potential marker of micrometastases and tumor vasculature and that it may play a role in the early incorporation of endothelial cells into small tumors as seeds for vasculogenesis. (biomedcentral.com)
  • The main approaches have been by antisense or small peptides specific against connexins. (ntu.edu.sg)
  • Connexins span the plasma membrane 4 times, with amino- and carboxy-terminal regions facing the cytoplasm. (novusbio.com)
  • The aim of this study was to investigate cumulus expansion, nuclear maturation and expression of connexin 43, cyclooxygenase-2 and FSH receptor transcripts in equine cumuli oophori during in vivo and in vitro maturation in the presence of equine FSH (eFSH) and precursors for hyaluronic acid synthesis. (biomedcentral.com)
  • We also discuss mechanisms of connexin influence and the role of individual connexins in various tissues and how these are affected in diabetes. (hindawi.com)
  • These results place an identified neuronal connexin in the context of a well-defined retinal circuit. (nih.gov)
  • Hartfield EM, Rinaldi F, Glover CP, Wong L-F, Caldwell MA, Uney JB (2011) Connexin 36 Expression Regulates Neuronal Differentiation from Neural Progenitor Cells. (plos.org)
  • To address this, we manipulated connexin protein expression via lentiviral transduction of mouse neuronal cortical cultures and analyzed neuronal death twenty-four hours following administration of NMDA (a model of NMDAR excitotoxicity) or oxygen-glucose deprivation (a model of ischemic injury). (ku.edu)
  • Taken together, these results suggest a role for neuronal gap junctions in cell death via a connexin type-independent mechanism that likely relies on channel activities of gap junctional complexes among neurons. (ku.edu)
  • Focal adhesion kinase modulates radial glia-dependent neuronal migration through connexin-26. (semanticscholar.org)
  • article{Valiente2011FocalAK, title={Focal adhesion kinase modulates radial glia-dependent neuronal migration through connexin-26. (semanticscholar.org)
  • Reduced connexin expression or modifications that affect gap-junctional conductance could impair conduction and lead to arrhythmias. (ahajournals.org)
  • Connexin 43 Mediated Gap Junctional Communication Enhances Breast Tumo" by Mary-Ann Pollmann, Qing Shao et al. (uwo.ca)
  • Total junctional conductance in Cx31 or Cx45 transfected cells is only about half as high as in other connexin transfectants analyzed and does not correlate exactly with any of the tracer permeabilities. (rupress.org)
  • They show overlapping tissue expression patterns, most tissues expressing more than one connexin type. (ebi.ac.uk)
  • Coexpression of connexins (Cx) has been demonstrated in a number of tissues including vascular smooth muscle 1 and myocardium. (ahajournals.org)
  • The answer to this question may be relevant to the understanding of gap junction function in tissues for which more than one connexin is expressed. (ahajournals.org)
  • De Bock M, Vandenbroucke RE, Decrock E, Culot M, Cecchelli R, Leybaert L (2014) A new angle on blood-CNS interfaces: a role for connexins? (springer.com)
  • These findings provide some molecular insights for essential roles of connexins and gap junctions in lens formation and the establishment and maintenance of lifelong lens transparency. (deepdyve.com)
  • These results indicate that quantitative and qualitative changes in connexin expression are associated with differentiation, migration and proliferation of keratinocytes in squamous epithelium. (oup.com)
  • BACKGROUND: The aim of this paper was to investigate the association between the connexin 37 (CX37) 1019C/T polymorphism and susceptibility to dilated cardiomyopathy (DCM). (minervamedica.it)