Connexins: 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.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.Connexin 43: 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.Cell Communication: 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.Lens, Crystalline: 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.Intercellular Junctions: 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)Eye ProteinsCarbenoxolone: 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.Ion Channels: 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.Oocytes: 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).Botany: The study of the origin, structure, development, growth, function, genetics, and reproduction of plants.Freeze Fracturing: 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.HeLa Cells: 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.Glycyrrhetinic Acid: 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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Ion Channel Gating: 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.Isoquinolines: 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)Zonula Occludens-1 Protein: A 195-kDa zonula occludens protein that is distinguished by the presence of a ZU5 domain at the C-terminal of the molecule.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Mitragyna: A plant genus of the family RUBIACEAE. Members contain antimalarial (ANTIMALARIALS) and analgesic (ANALGESICS) indole alkaloids.Astrocytes: 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.Molecular Sequence Data: 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.Xenopus laevis: 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.Microscopy, Confocal: 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.Heptanol: A colorless liquid with a fragrant odor. It is used as an intermediate, solvent and in cosmetics.Encyclopedias as Topic: 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)Mutation: 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.Chemokine CX3CL1: 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.Patch-Clamp Techniques: 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.Sucrose: 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.Membrane Potentials: 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).Potassium Channels: 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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Antibodies: 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).Antibody Specificity: 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.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Wheat Germ Agglutinins: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Triticum: 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.Neurons: 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.Neurogenesis: Formation of NEURONS which involves the differentiation and division of STEM CELLS in which one or both of the daughter cells become neurons.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.Platelet Aggregation: The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Platelet Function Tests: Laboratory examination used to monitor and evaluate platelet function in a patient's blood.Platelet Count: The number of PLATELETS per unit volume in a sample of venous BLOOD.

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 - 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 ...
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. ...
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 ...
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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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 ...
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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 ...
Pannexin1 (Panx1) forms nonselective membrane channels, structurally similar to gap junction hemichannels, that is permeable to ions, nucleotides and other small molecules below 900 Da. Panx1 activity is implicated in paracrine signaling and inflammasome regulation. Recent studies in different animal models showed that Panx1 overactivation correlates with a selective demise of several types of neurons, including retinal ganglion cells, brain pyramidal and enteric neurons. The list of Panx1 activators includes extracellular ATP, glutamate, high K+, Zn2+, fibroblast growth factors (FGFs), pro-inflammatory cytokines and elevation of intracellular Ca2+. Most of these molecules are released following mechanical, ischemic or inflammatory injury of the CNS, and rapidly activate this channel. As a result, prolonged opening of Panx1 channel induced by these
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. ...
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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 - 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 ...
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
A gap junction may also be called a nexus or macula communicans. When found in neurons or nerves it may also be called an electrical synapse. While an ephapse has some similarities to a gap junction, by modern definition the two are different. Gap junctions are a specialized intercellular connection between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulated gate between cells. One gap junction channel is composed of two connexons (or hemichannels), which connect across the intercellular space. Gap junctions are analogous to the plasmodesmata that join plant cells. Gap junctions occur in virtually all tissues of the body, with the exception of adult fully developed skeletal muscle and mobile cell types such as sperm or erythrocytes. Gap junctions, however, are not found in simpler organisms such as sponges and slime molds. In vertebrates, gap junction hemichannels are ...
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 Vitorin, Jose 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 ...
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 ...
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 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 ...
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...
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 ...
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Propagating Ca2+ signals in the cochlea (Gale et al., Current Biology, 14: 526-529, 2004), depend on ATP release at the endolymphatic surface of the neurosensory epithelium and have been recently linked by others to the development of afferent synapses in the cochlea (Tritsch NX et al., Nature, 450: 50, 2007). Using four types of genetically targeted mice, we show unequivocally that Connexin 26 (Cx26) and connexin (Cx30), the two most abundant connexins in the inner ear, contribute in two strictly interdependent ways to the generation and propagation of cochlear Ca2+ waves, acting as conduits for both ATP and second messengers. Cx26 and Cx30 are encoded by two genes (GJB2 and GJB6, respectively) that are found within 50 kb in the same complex deafness locus, named DFNB1. By showing that a specific defect of Cx26 affects metabolic coupling mediated by IP3 we have recently offered a mechanistic explanation for the pathogenesis of deafness due to connexin mutations (Beltramello et al, Nature Cell ...
Diseases of the blood vessels and heart have the highest mortality rates in the world. In advanced disease, critical blood vessels can become blocked by a build-up of cells and lipids within the walls of the blood vessel. This can severely limit blood flow to affected organs such as the heart and is a major cause of high blood pressure, heart attacks and stroke. Treatments include surgery to restore blood flow by re-widening of the blood vessels by balloon catheter and permanent placement of a metal supports called stents or by blood vessel bypass. These surgeries can alleviate symptoms but cause blood vessel damage that promotes surrounding cells to divide and blood vessel re-narrowing in a high number of patients. We have recently identified that proteins called connexins, found in all blood vessel cells, are directly linked to the regulation of cell division. My work focuses on identifying the impact of specific connexin proteins in blood vessel disease, defining how they interact with ...
One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
To couple an in vitro cardiomyocyte with a computational model of a cardiac cell, membrane potential is recorded from the patch-clamped cell, while the membrane potential of the model is computed in real-time. A gap junctional current is then calculated and injected into the in vitro cardiomyocyte via the amplifier. The end result is real-time electrical interactions between the two "cells" as if an intercellular gap junction physically coupled them.. ...
The protein encoded by this gene belongs to the innexin family. Innexin family members are the structural components of gap junctions. This protein and pannexin 2 are abundantly expressed in central nerve system (CNS) and are coexpressed in various neuronal populations. Studies in Xenopus oocytes suggest that this protein alone and in combination with pannexin 2 may form cell type-specific gap junctions with distinct properties. [provided by RefSeq, Jul 2008 ...
The ARC Centre of Excellence in Coherent X-ray Science (CXS) is an Australian government initiative that began in July 2005 to explore what can be achieved with X-ray optics; including an understanding of exotic phenomena such as X-ray phase discontinuities.
Nel corso di questo lavoro, abbiamo osservato che le cellule cocleari non-sensoriali che compongono il greater and lesser epithelial ridge (GER e LER, rispettivamente) condividono la stessa cascata di trasduzione del segnale attivato da ATP dipendente da PLC e IP3R. Inoltre, abbiamo dimostrato che lattività dei segnali Ca2+ ATP-dipendente nelle cellule cocleari non-sensoriale è spazialmente ordinata dallapice alla base della coclea durante la prima settimana postnatale. Il segnale di Ca2+ in queste condizioni dipende della generazione delinositolo-1,4,5-trifosfato a partire dellidrolisi di PI(4,5)P(2) dipendente da PLC. Abbiamo quindi analizzato dei topi con espressione difettosa di PIPKIγ e abbiamo mostrato che (i) tale enzima è essenziale per lacquisizione delludito, (ii) è responsabile principalmente della sintesi di pool di PI(4,5)P(2) regolati da recettore e sensibili a PLC nei sincizi cellulari che fanno da supporto alle cellule ciliate uditive, e che (iii) la diminuzione ...
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Shop Gap junction delta-2 protein ELISA Kit, Recombinant Protein and Gap junction delta-2 protein Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
Calcium, Cell Communication, Communication, Concentration, Connexins, Diseases, Gap Junction, Ions, Isoforms, Membrane, Membrane Potential, Mutations, Pharmacology, Second Messengers, Therapeutic
Easy to read patient leaflet for Maxi-Tuss HCX liquid. Includes indications, proper use, special instructions, precautions, and possible side effects.
Complete information for GJB5 gene (Protein Coding), Gap Junction Protein Beta 5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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Lets look at E. coli for a moment just to get an idea of its size, and also to get an idea of the sizes of various molecules. Figure 1.25 [overhead- E. coli cell x 100,000] is an artists rendition of a typical E. coli cell, with the various components drawn to scale. Figure 1.26 [overhead- E. coli cytosol] magnifies a square section of that cell another ten times so that particles such as ribosomes, proteins and DNA are readily visible. This view leaves out all of the small molecules though, to simplify the visualization. Finally a corner of the square is magnified a further ten times and water and small metabolites are shown in a very thin slice of our bacterial cell.. Cool facts about E. coli :70% water, 15% protein, 7% nucleic acids, 3% polysaccharides, 3%, lipids, 1% inorganic ions, & 0.2% metabolites.. ...
Pathogenic variants in the gap junction protein beta-2 (GJB2) gene are the most common cause of hearing loss. Of these, the p. V37I variant of GJB2 has a high ...
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Receptor activator of NF-kappaB ligand (RANKL) is crucial in osteoclastogenesis but signaling events involved in osteoclast differentiation are far from complete and other signals may play a role in osteoclastogenesis. A more direct pathway for cellular crosstalk is provided by gap junction intercellular channel, which allows adjacent cells to exchange second messengers, ions, and cellular metabolites. Here we have investigated the role of gap junction communication in osteoclastogenesis in mouse bone marrow cultures. Immunoreactive sites for the gap junction protein connexin 43 (Cx43) were detected in the marrow stromal cells and in mature osteoclasts. Carbenoxolone (CBX) functionally blocked gap junction communication as demonstrated by a scrape loading Lucifer Yellow dye transfer technique. CBX caused a dose-dependent inhibition (significant , or = 90 microM) of the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells formed in 7- to 8-day marrow cultures ...
Reversible down-regulation of gap junctional intercellular communication (GJIC) is proposed to be an important cellular mechanism in tumor promotion. Gap junction function is modified by a variety of tumor promoters, including the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Treatment of cells with TPA results in the activation and subsequent depletion of the TPA-responsive protein kinase C (PKC) isoforms. TPA-induced degradation of the PKC isoforms α, δ and ϵ was recently shown to occur via the ubiquitin-proteasome pathway. In the present study we investigated the role of the proteasome in the TPA-induced modification of GJIC in IAR20 rat liver epithelial cells. TPA exposure of IAR20 cells induced hyperphosphorylation of gap junction protein connexin43 and inhibition of GJIC. Prolonged TPA treatment induced down-regulation of PKCα, δ and ϵ and a reduction in the total PKC activity, which was associated with recovery of GJIC. Co-treatment of IAR20 cells with TPA and the ...
PURPOSE To establish an electrical fingerprint for the gap junction channels between mammalian lens epithelial cells. METHODS The double whole cell patch clamp technique was applied to isolated cell pairs obtained from mouse lens epithelium and a continuous cell line of lens epithelial cells derived from the sheep lens (SLE 2.1). RESULTS The junctional conductance in mouse lens epithelial cells and in cultured SLE 2.1 cells was found to be moderately voltage dependent. SLE 2.1 cells were analyzed in more detail. The voltage dependence could be described by a Boltzmann distribution with Vo = +/- 63.1 mV and Gmin = 0.34. In cell pairs that exhibited spontaneously low junctional conductance, single channel events could be distinguished. Single gap junction channel currents had a linear current-voltage relationship. A frequency histogram of single channel conductances from eight cell pairs had three major peaks of 35, 60 and 97 pS. CONCLUSION The electrical properties of gap junction channels
Read "Connexin Composition in Apposed Gap Junction Hemiplaques Revealed by Matched Double-Replica Freeze-Fracture Replica Immunogold Labeling, The Journal of Membrane Biology" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
The usage of stem cells is a promising strategy for the repair of damaged tissue in the injured brain. Recently, amniotic fluid (AF) cells have received a lot of attention as an alternative source of stem cells for cell-based therapies. However, the
Introduction: Metastasis involves the emigration of tumor cells through the vascular endothelium, a process also known as diapedesis. The molecular mechanisms regulating tumor cell diapedesis are poorly understood, but may involve heterocellular gap junctional intercellular communication (GJIC) between tumor cells and endothelial cells. 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. Results: HBL100 cells expressing Cx43 formed functional heterocellular gap junctions with HMVEC monolayers within 30 minutes. In addition, immunocytochemistry revealed Cx43 localized to contact sites between Cx43 expressing tumor cells and endothelial cells. Quantitative analysis of diapedesis revealed a two-fold increase in diapedesis of Cx43 expressing
Gap junctions are specialized cell-cell contacts that provide direct intercellular communication between eukaryotic cells. The tyrosine-sorting signal (YXXØ), present at amino acids 286-289 of Cx43 (connexin43), has been implicated in the internalization of the protein. In recent years, ubiquitination of Cx43 has also been proposed to regulate gap junction intercellular communication; however, the underlying mechanism and molecular players involved remain elusive. In the present study, we demonstrate that ubiquitinated Cx43 is internalized through a mechanism that is independent of the YXXØ signal. Indeed, expression of a Cx43-Ub (ubiquitin) chimaera was shown to drive the internalization of a mutant Cx43 in which the YXXØ motif was eliminated. Immunofluorescence, cycloheximide-chase and cell-surface-protein biotinylation experiments demonstrate that oligomerization of Cx43-Ub into hemichannels containing wild-type Cx43 or mutant Cx43Y286A is sufficient to drive the internalization of the ...
Purpose: Cancer patients are often concurrently treated with analgesics and antineoplastic drugs, yet the influence of analgesic agents on therapeutic activity of antineoplastic drugs is largely unexplored. This study investigates the effects of three commonly used analgesics, which produce analgesia by different mechanisms, on cytotoxicity induced by cisplatin, a widely used antitumor agent, and the relation between those effects and modulation of gap junction function by the analgesics.. Experimental Design: The role of gap junctions in the modulation of cisplatin toxicity is explored by manipulation of connexin expression, and gap junction presence and function, using clinically relevant concentrations of the analgesics and cisplatin.. Results: Short-term exposure of transformed cells to cisplatin reduced the clonogenic survival in low-density cultures (without gap junction formation) and in high density (with gap junction formation), but the toxic effect was greater at high density. In the ...
There is a reduction in the 28-kD gap junction protein detectable by immunofluorescence in livers of partially hepatectomized rats and in cultured hepatocytes stimulated to proliferate. By the coordinate use of antibodies directed to the hepatic junction protein (HJP28) and the use of a monoclonal antibody that recognizes bromodeoxyuridine (BrdU) incorporated into DNA, we have been able to study the relationship between detectable gap junction protein and cell division. Hepatocytes that label with BrdU in the regenerating liver and in cell culture show a significant reduction of HJP28. Cells that do not synthesize DNA, on the other hand, show normal levels and distribution of immunoreactive gap junction protein. We postulate that the quantitative changes in gap junction expression might play an important role in the control of proliferation in the liver.
Several laboratories have demonstrated a decrease in gap junctional communication in cells transformed by the src oncogene of the Rous sarcoma virus. The decrease In gap junctional communication was associated with tyrosine phosphorylation of the gap junction protein, connexin43 (Cx43). This study was initiated to determine if the phosphorylation of Cx43 is the result of a direct kinase-substrate interaction between the highly active tyrosine kinase, pp60v-src, and Cx43. Confocal microscopy data indicates that the two proteins are within physical proximity allowing for a potential kinase-substrate interaction. Previous biochemical studies have been limited by the low levels of Cx43 protein in fibroblast cell lines. To obtain larger quantities of Cx43 we constructed a recombinant baculovirus expressing Cx43 in Spodoptera frugiperda (Sf-9) cells and subsequently purified the expressed Cx43 by immunoaffinity chromatography. We observed that this partially-purified Cx43 was phosphorylated on ...
Despite the high number of identified loci for autosomal recessive nonsyndromic HIH, the majority of cases (58-88%) are linked to DFNB1 on the chromosome 13q12 and are due to mutations in the GJB2 gene (MIM 121011), which encodes the gap junction protein connexin 26. The 35delG mutation in the GBJ2 gene is the commonest mutation in Caucasian populations. Its carrier frequency is 1 per 35 in Southern Europe and 1 per 79 in Central and Northern Europe. Mutation analysis of 35delG mutation in the GJB2 gene is available as a genetic diagnostic test. Unlike several forms of congenital deafness, GJB2-related deafness has no known comorbidity. Knowing the mutation status at the outset in a child with hearing impairment will save the time, effort and cost involved in performing different investigations.. ...
Gap junction (GJ)*proteins (termed connexins [Cxs]), comprise a family of vertebrate transmembrane proteins that assemble intracellularly to form oligomeric channels (Musil and Goodenough, 1993). The GJ hemichannels, or connexons, are transported to the plasma membrane where they dock with connexons in the membranes of adjacent cells and aggregate to mediate intercellular transfer of various ions, signaling molecules, and metabolites (Simon and Goodenough, 1998). The essential role of GJ communication in the coordination of physiological processes within various tissues has become increasingly apparent, with defects in the different Cx proteins now linked to a wide variety of pathological conditions (Krutovskikh and Yamasaki, 2000).. The GJ protein Cx43 is one of the more ubiquitous of the GJ proteins. Its importance is underscored by the abnormal heart development, perinatal mortality, female sterility, altered bone development, and cataracts observed in Cx43 knockout (KO) mice (Lo, 1999). Its ...
Purpose: : The purpose of this study is to determine the PKCγ phosphorylation site on Cx50 in lens epithelial cells and subsequent functional results of phosphorylation. Methods: : Mutation (S430A) was introduced into the wild type Cx50:EGFP by site-directed mutagenesis. Wild-type and mutated (S430A) Cx50 were transfected into 80% confluent N/N lens epithelial cells, and stably transfected cells were selected in DMEM media. PKCγ was activated by phorbol-12 myristate 13 acetate (TPA, 200nM). Expression and localization of wild type and mutated Cx50-EGFP fusion proteins before and after TPA treatment were measured by confocal microscopy. Cell surface Cx50 gap junction plaques were immuno-labeled and counted by confocal microscopy. Co-localization of Cx50 and PKCγ was determined by co-immunoprecipitation. Phosphorylation of Cx50-S430 was determined by western blotting with anti-phosphoserine antibodies and functional effects were measured by gap junction plaque assembly-disassembly. Results: : ...
TY - JOUR. T1 - Colocalization of connexin 43 and connexin 45 but absence of connexin 40 in granulosa cell gap junctions of rat ovary. AU - Okuma, A.. AU - Kuraoka, A.. AU - Iida, H.. AU - Inai, T.. AU - Wasano, K.. AU - Shibata, Y.. PY - 1996/7. Y1 - 1996/7. N2 - The expression and localization of gap junction family proteins (connexins) were examined in nonstimulated and gonadotrophin-stimulated ovarian follicles of immature rats. Immunoblot and RNA blot analysis showed the presence of connexin (Cx) 43, Cx40 and Cx45 in ovarian tissue. Of these connexin proteins, Cx43 and Cx45 were identified by immunofluorescent microscopy between granulosa cells in characteristic expression patterns related to follicular developmental stages, while Cx40 was not expressed in granulosa cells but was detected in blood vessels in ovarian stroma. In some plaques of gap junction between granulosa cells, Cx45 was found to be colocalized with Cx43. In immunofluorescent microscopy, the expression of Cx43 was ...
The molecular basis of gap junctions in invertebrates has been a mystery for decades. Connexin proteins were first identified in the 1970s as the structural components of gap junctions in vertebrates (Goodenough, 1974). For more than 20 years, the term `connexin became synonymous with gap junctions, whereas efforts to find the homologous connexin in invertebrates were unsuccessful (Phelan et al., 1998). It was only in 1998 that the gene family encoding invertebrate gap-junction proteins, innexins, was first confirmed in Drosophila (Phelan et al., 1998). To date, eight innexin genes have been found in the fruit fly, and 25 innexin genes in C. elegans (Phelan, 2005).. In the present study we identify six innexin-like genes in Aedes (Table 5). The neighbor-joining tree (Fig. 9) shows that most of the innexins in Aedes are still closely related to their Drosophila homologues despite the 250 million years of evolution that separate the mosquito from the fruit fly (Severson et al., 2004). The strong ...
In the present study we demonstrated, by various experimental approaches, that cAMP and PKC are involved in the modulation of inter-TEC GJIC: the cAMP agonist 8-Br-cAMP enhanced inter-TEC coupling whereas PMA-induced PKC activation triggered an opposite effect.. Using flow cytometry we first detected in a mouse TEC line, that up to 90% of DiIc18(3)+ cells co-cultured in 1:1 ratio with calcein+ cells became double positive, a phenomenon which was readily inhibited by the gap junction inhibitors 18-β-glycyrrhetinic acid and carbenoxolone. This result clearly demonstrates that the thymic epithelium spontaneously forms a GJIC-dependent functional syncytium in vitro. Under these conditions, 8-Br-cAMP and forskolin did not significantly modify this spontaneous percentage of coupled cells. However, both compounds enhanced up to 3 fold the calcein fluorescence intensity of the double positive cells, indicating an increase in the rate of dye transfer among coupled cells. Importantly, 8-Br-cAMP also ...
The work presented in this thesis describes the influence of the endothelium on smooth muscle cells, and how the structure of the internal elastic lamina (IEL) affects this relationship in mesenteric and saphenous arteries. This was enabled by the study of functional and confocal microscopy dye transfer experiments. Normotensive (WKY) and hypertensive (SHR) rats of 12 weeks and 6 months of age were used to assess the effect of hypertension and ageing on endothelial and smooth muscle cell communication. The endothelium-derived hyperpolarising factor (EDHF) response in mesenteric arteries was investigated using wire myography, and the involvement of myoendothelial gap junctions (MEGJs) was assessed using the putative gap junction inhibitor carbenoxolone. Carbenoxolone attenuated the EDHF response in the WKY, suggestive of the involvement of myoendothelial gap junctions in EDHF. In the saphenous artery, incubation with L-NAME and indomethacin abolished the relaxation to ACh, indicating that there ...
A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases ...
The post-vitellogenic oocytes of teleost fish are generally unresponsive to maturation-inducing hormone (MIH) until a luteinizing hormone (LH) surge stimulates sensitivity via the acquisition of oocyte-maturational competence (OMC). Heterologous gap junctions (GJs) between granulosa cells and the oocyte have been previously implicated in the regulation of oocyte maturation in various vertebrate species. Although heterologous GJ are present in ovarian follicles of ayu (Plecoglossus altivelis), their role in maturation remains unclear. In the present study, we cloned and characterized complementary DNAs for GJ protein connexin (Cx), and examined the expression pattern of Cx messenger RNAs in the ayu ovary. Four Cx cDNAs with predicted molecular masses of 32.1 (Cx32.1), 34.9 (Cx34.9), 44.1 (Cx44.1), and 44.2 (Cx44.2) kDa, respectively, were cloned. Northern blot analysis revealed that the levels of Cx44.1 and Cx44.2 transcripts were similar during the vitellogenic and ovulatory stages. Cx32.1 transcripts
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] ...
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] ...
The modified residue is found at amino acid 400 of the final protein. This is located in the sixth transmembrane region found, which corresponds to the inner vestibule of the pore. A stem loop hairpin structure mediates the RNA editing. ADAR2 is likely to be the preferred editing enzyme at the I/V site. Editing results in a codon alteration from ATT to GTT, resulting in an amino acid change from isoleucine to valine. ADAR2 enzyme is the major editing enzyme. The MFOLD programme predicted that the minimum region required for editing would form an imperfect inverted repeat hairpin. This region is composed of a 114 base pairs. Similar regions have been identified in mouse and rat. The edited adenosine is found in a 6-base pair duplex region. Mutation experiment in the region near the 6-base pair duplex have shown that the specific bases in this region were also essential for editing to occur. The region required for editing is unusual in that the hairpin structure is formed by exonic sequences ...
Voltage-dependent calcium channel subunit alpha2delta-2 is a protein that in humans is encoded by the CACNA2D2 gene.[5] This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene, encoding different isoforms, have been characterized.[5] CACNA2D2 containing channels are blocked by amiodarone.[6] ...
One connexin protein has four transmembrane domains. *6 Connexins create one Connexon (hemichannel). When different connexins ... By study of connexins still in membranes lipids associated with the connexins have been studied.[124] It was found that ... Innexins have no significant sequence homology with connexins.[8] Though differing in sequence to connexins, innexins are ... In turn, hemichannels of uniform connexin composition are called homomeric, while those with differing connexins are ...
connexin complex. • endoplasmic reticulum membrane. • endoplasmic reticulum. • membrane. • lateral plasma membrane. Biological ... Gap junction beta-1 protein (GJB1), also known as connexin 32 (Cx32) is a transmembrane protein that in humans is encoded by ... Andrew L Harris; Darren Locke (2009). Connexins, A Guide. New York: Springer. p. 574. ISBN 978-1-934115-46-6.. ... GJB1 is a gap junction, beta 1 protein also identified as connexin 32, with 238 amino acids.[7] This protein contains four ...
Abrams, Charles K.; Rash, John E. (2009). "Connexins in the Nervous System". In Harris, Andrew; Locke, Darren. Connexins. New ...
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 ... 2000). "Mutation in the gene for connexin 30.3 in a family with erythrokeratodermia variabilis". Am. J. Hum. Genet. 67 (5): ... 1992). "Two gap junction genes, connexin 31.1 and 30.3, are closely linked on mouse chromosome 4 and preferentially expressed ...
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". ...
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, C. B.; Harris, K. C.; Runge-Samuelson, C. L.; Flanary, V. A.; Wackym, P. A. (2004). "Connexin 26 and Connexin 30 ...
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.; ...
Connexin-43 is a 43.0 kDa protein composed of 382 amino acids. GJA1 contains a long C-terminal tail, an N-terminal domain, and ... 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 ...
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 ... Wei CJ, Xu X, Lo CW (2004). "Connexins and cell signaling in development and disease". Annu. Rev. Cell Dev. Biol. 20: 811-38. ... Connexon pores vary in size, polarity and therefore can be specific depending on the connexin proteins that constitute each ... ISBN 1-4160-2973-7. Andrew L Harris; Darren Locke (2009). Connexins, A Guide. New York: Springer. p. 574. ISBN 978-1-934115-46- ...
... , 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) and is a protein ... "Entrez Gene: GJA9 gap junction protein, alpha 9, 36kDa". Andrew L Harris; Darren Locke (2009). Connexins, A Guide. New York: ...
Probenecid did not affect channels formed by connexins. Panchin Y, Kelmanson I, Matz M, Lukyanov K, Usman N, Lukyanov S (2000 ... Structurally, pannexins and connexins are very similar, consisting of 4 transmembrane domains, 2 extracellular and 1 ... 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 ... Gap junction beta-2 protein (GJB2), also known as connexin 26 (Cx26) - is a protein that in humans is encoded by the GJB2 gene ... Connexin Gap junction Vohwinkel syndrome Bart-Pumphrey syndrome GRCh38: Ensembl release 89: ENSG00000165474 - Ensembl, May 2017 ... "Entrez Gene: GJB2 gap junction protein, beta 2, 26kDa". Kenneson A, Van Naarden Braun K, Boyle C (2002). "GJB2 (connexin 26) ...
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): ...
Andrew L. Harris; Darren Locke (2009). Connexins, a guide. New York: Springer. p. 574. ISBN 978-1-934115-46-6. Haas JS, Zavala ...
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- ... Gap junction proteins with no sequence homology to connexins were initially identified in fruit flies. It was suggested that ... Structurally, pannexins are similar to connexins. Both types of protein consist of a cytoplasmic N-terminal domain, followed by ...
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 ...
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. ...
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 ...
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 ... 2001). "Expression of connexin 43 and connexin 32 gap-junction proteins in epilepsy-associated brain tumors and in the ... 2005). "Connexin-47 and connexin-32 in gap junctions of oligodendrocyte somata, myelin sheaths, paranodal loops and Schmidt- ...
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 ...
... 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 ...
  • 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)
  • 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)
  • Connexin 26 is a protein establish on the GJB2 gene which mostly relates as the cause of congenital hearing loss . (biology-online.org)
  • Defects in this gene lead to the most common form of congenital deafness in developed countries, called DFNB1, also known as Connexin 26 deafness or GJB2-related deafness.Gap junctions were first characterized by electron microscopy as regionally specialized structures on plasma membranes of contacting adherent cells. (cloud-clone.com)
  • Future research could be directed at achieving ways of optimising and modulating connexin expression as a therapeutic tool. (kup.at)
  • 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)
  • 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)
  • (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)
  • 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)
  • 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)
  • 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)
  • Thus, connexins differ in their ability to form functional heterotypic gap junctions among mammalian cells. (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)
  • GJA9, also called connexin-36 (CX36), is a member of the connexin gene family that is expressed predominantly in mammalian neurons. (thermofisher.com)
  • 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)
  • Is the connexin 26 gene (causes deafness) passed down from generations? (healthtap.com)
  • The logo of the Connexin-deafness page is a photograph of a staircase of a campanile in the expiatory temple of the Sagrada Familia by Gaud in Barcelona. (crg.es)
  • 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)
  • 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)
  • Connexins are expressed in many different tissues. (crg.es)
  • 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)
  • 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)
  • 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)
  • 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)
  • Connexins are commonly named according to their molecular weights, e.g. (wikipedia.org)
  • Connexin 26 transcript holds a putative mRNA volatility sequence which has 226 amino acid protein that has a molecular mass of about 26 kD and is assigned to human chromosome 13q11-q12. (biology-online.org)
  • 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)
  • 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)
  • The connexins are designated by their molecular mass. (cloud-clone.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)
  • The main approaches have been by antisense or small peptides specific against connexins. (ntu.edu.sg)
  • 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)
  • Connexins span the plasma membrane 4 times, with amino- and carboxy-terminal regions facing the cytoplasm. (novusbio.com)
  • Here we used this approach to show that newly synthesized connexin43 was transported predominantly in 100- to 150-nanometer vesicles to the plasma membrane and incorporated at the periphery of existing gap junctions, whereas older connexins were removed from the center of the plaques into pleiomorphic vesicles of widely varying sizes. (sciencemag.org)
  • 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)
  • 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 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)
  • 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)
  • 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)
  • There are two types of connexins, alpha and beta, named GJA or GJB followed by a number. (crg.es)
  • 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)
  • 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)
  • 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)
  • 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)
  • Connexins are, for the most part, highly regulatable molecules. (ahajournals.org)
  • We compare the permeabilities of gap junctions comprised of different connexins to iontophoretically injected tracer molecules. (rupress.org)
  • onditional Lyz2 cre/cre Gja1 flox/flox mice were developed to specifically assess Connexin-43 impact in macrophages. (elifesciences.org)
  • 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)
  • 21 members of the connexin gene family are likely to be expressed in the human genome. (eurekaselect.com)