Role of connexins. Medical search. Frequent questions

Connexins (Cx) are primary components of gap junctions, selectively allowing molecules to be exchanged between adjacent cells. (iyte.edu.tr)
Along with their channel forming functions, connexins play variety of roles in different stages in tumorigenesis, both dependent and independent of gap junctions in connexin and cancer dependent manner. (iyte.edu.tr)
Connexins form gap junctions, clusters of intercellular channels synchronizing responses in multi-cellular organisms through the direct exchange of ions, small metabolites and second messengers between adjacent cells. (unige.ch)
Gap junctions play an important regulatory role in various physiological processes including signal propagation in cardiac muscles and tissue homeostasis of the liver. (wikipedia.org)
Calmodulin (CaM) is a protein composed of 148 amino acids that plays both an intermediary and direct role in moderating gap junctions. (wikipedia.org)
Connexin (Cx) and pannexin (Panx) containing channels - gap junctions (GJs) and hemichannels (HCs) - are present in virtually all cells and tissues. (utmb.edu)
Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. (medlineplus.gov)
Gap junctions made with connexin 26 transport potassium ions and certain small molecules. (medlineplus.gov)
Lastly, we used RNA knockdown methods to diminish the expression of connexin proteins, which generate so-called "gap junctions" between cells - channels of communication which calcium and other molecules can traverse. (uib.no)
Thus, we can now propose that intricately choreographed calcium signaling through gap junctions plays a pivotal role in steering the early development of the embryo. (uib.no)
Canonically, connexins form gap junctions that allow the passage of ions and small molecules between cells. (warwick.ac.uk)
Keywords: Connexin Gap junction Hemichannel Independent function 1 Introduction Connexins are proteins which form both gap junctions and hemichannels which are ubiquitously found in both vertebrates and invertebrates. (liveconscience.com)
PCI-34051 and the permeability and signaling properties of the individual gap junctions and hemichannels are defined by their specific connexins. (liveconscience.com)
Since then there has been a surge of studies dedicated to discovering the role of gap junctions and connexins in tumor progression [5 12 Reduced expression of connexins and GJIC has been shown in many tumor types and connexins have been recognized as tumor suppressors. (liveconscience.com)
[ 5 ] Connexins (markers for the presence of gap junctions) are present in the oral mucosa of patients with recurrent aphthous ulcers (canker sores) in amounts similar to those present in normal mucosal tissue. (medscape.com)
We are studying the role of the ubiquitin system in the regulation of connexins and how the malfunction of these processes may contribute to the loss of intercellular communication via gap junctions during cancer pathogenesis. (ous-research.no)

The gap-junction proteins connexin (Cx) 43 and Cx26 increased. (yonsei.ac.kr)
They are formed by two hemichannels, made up of six connexin proteins assembled in groups. (nih.gov)
The specificity of the gap junction is determined by which connexin proteins comprise the hemichannel. (nih.gov)
This gene encodes one of the connexin proteins. (nih.gov)
The altered protein probably disrupts the function of normal connexin 26 in cells, and may interfere with the function of other connexin proteins. (medlineplus.gov)
Calcium plays an important role in this communication, because it exerts regulatory effects on many cellular proteins and cellular processes. (uib.no)
Scientific background Connexins (Cx) are integral membrane proteins consisting of four transmembrane domains, two extracellular loops, one intracellular loop and intracellular N- and C-termini. (alomone.com)
Connexins a family of transmembrane proteins are components of both gap junction channels and hemichannels which mediate the exchange of ions and small molecules between adjacent cells and between the inside and outside of the cell respectively. (liveconscience.com)
A plethora of connexin-associated proteins have been discovered including cytoskeletal elements enzymes adhesion molecules and signaling molecules. (liveconscience.com)
These connexin-associated proteins are shown to regulate a number of mechanisms involved in IMPA2 antibody both channel-dependent and independent functions by connexins [8-10]. (liveconscience.com)
In vertebrates, gap junction channels are composed of members of a family of integral membrane proteins known as connexins. (ous-research.no)
Several members of the connexin protein family have been shown to act as tumor suppressor proteins, and they are frequently downregulated during cancer development. (ous-research.no)
7] Connexins are a family of transmembrane proteins that assemble into hexameric hemichannels and form gated intercellular gap junction channels. (medscape.com)
Now a large and ever increasing number of genetic subtypes has been described, and major advances in molecular and cellular biology have clarified the understanding of the role of different proteins in the physiology of peripheral nerve conduction in health and in disease. (medscape.com)

The GJB2 gene mutations that cause Vohwinkel syndrome change single protein building blocks (amino acids) in connexin 26. (medlineplus.gov)
His laboratory is interested in investigating the pathophysiology and genetics of hearing loss associated with mutations in Connexin 26, the most commonly affected gene in congenital hearing loss, and the development of gene therapy for hearing restoration. (ucsf.edu)
To elucidate the mechanisms by which connexin mutations lead to cataracts, we have been studying mouse models that mimic the mutations identified in human pedigrees with inherited congenital cataracts. (molvis.org)
Among the various types of connexins mutations or loss of PCI-34051 functional channels are implicated in many diseases and disorders such as congenital deafness skin disorders cataracts and cancers [4 5 Intriguingly some disease-causing mutants of connexins form functional channels [4] as those formed by wild-type connexins which implies channel-independent roles of connexins. (liveconscience.com)
Molecular diagnostic testing for mutations in the connexin genes GJB3,GJB4, and GJA1 is available. (medscape.com)

In contrast to the atherogenic role of Cx43, Cx37 hemichannels in macrophages and endothelial Cx40 gap junction channels are atheroprotective. (unige.ch)
More recently, genetic and pharmacologic studies revealed the role of connexins, and in particular Cx43, in the differentiation and function of all bone types. (biomedcentral.com)
Interestingly, these same connexins (Cx46, Cx45 and Cx43) are all found in the bone where they have the potential to create different types of channels with unique abilities to pass ions and small molecules as well as be regulated by pH, voltage, and posttranslational modifications [ 8 ]. (biomedcentral.com)
Less is known about the role of Cx43 in other cell types during bone development. (biomedcentral.com)
Western blot analysis showed that connexin 43 (Cx43), which is the major functional protein of gap junction, is present in multiphosphorylated forms: a nonphosphorylated form (P0) and phosphorylated forms (P1, P2, and P3). (elsevierpure.com)
In rare cases, pathogenic missense changes in the GJA1 gene encoding connexin-43 (Cx43) have been reported. (medscape.com)

Pannexins, molecules with similar structure and single-membrane channel forming potential as connexins when organized as hemichannels, are also expressed in osteoblastic cells. (biomedcentral.com)
Connexin (Cx) complexity: Cxs oligomerize to form hemichannels (connexons) that are transported to the cell surface where they dock with hemichannels from a contacting cell to form intercellular gap junction channels [ 1 ]. (biomedcentral.com)

Gap junction channels are even more complex as connexin subunits can form homomeric or heteromeric arrangements that dock across the extracellular space to form homo- or heterotypic channels. (biomedcentral.com)
We are also exploiting evolution of connexins to devise chimaeric modified connexin subunits that can coassemble with endogenously expressed connexins to remove CO 2 sensitivity very selectively allowing us to further probe physiological function. (warwick.ac.uk)

Currently, the role of these channels under physiological conditions is well defined. (utmb.edu)
This review covers some of the most striking microRNA functions involved in morphine tolerance and presents limitations on our knowledge of their physiological roles. (hindawi.com)
Our focus is on further understanding (via cryoEM, with Prof Alex Cameron) the structural biology of how CO 2 causes conformational change in these connexins and elucidating further physiological functions of connexin mediated CO 2- signalling such as hypercapnic arousal reflexes (with Prof Mark Wall). (warwick.ac.uk)

Each connexin protein has four transmembrane segments, two extracellular loops, a cytoplasmic loop formed between the two inner transmembrane segments, and the N- and C-terminus both being in the cytoplasm. (nih.gov)

This gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. (medlineplus.gov)
In large families, the disorder was mapped to a connexin gene cluster at band 1p34.3. (medscape.com)
The T-box gene family is a group of related genes that play a critical role in human embryonic development. (medscape.com)

The research team was able to show that the network interfaces are created by a certain molecule, connexin 43, that is able to form pores. (sciencedaily.com)
A decade ago, Gourdie and his lab developed the study's connexin 43-targeting molecule, alphaCT1. (eurekalert.org)

These intercellular channels formed from connexins are present in bone forming osteoblasts, bone resorbing osteoclasts, and osteocytes (mature osteoblasts embedded in the mineralized bone matrix). (biomedcentral.com)

Synchrony between neighboring neurons depends on the protein connexin 36, an essential element of certain types of synaptic connections that, unlike classical chemical synapses, pass signals between neurons through direct electrical connections. (cureepilepsy.org)
As an essential component of electrically coupled synapses between neurons, connexin 36 plays an important role in rapid and synchronous activation of interconnected neworks of neurons within the brain, which is necessary for normal brain processes. (cureepilepsy.org)

Approximately two thirds of cases of EKVP are caused by heterozygous missense variants in the connexin genes GJB3, encoding connexin-31 (Cx31), and GJB4, encoding connexin-30.3 (Cx30.3). (medscape.com)

Valdebenito, S, Barreto, A & Eugenin, EA 2018, ' The role of connexin and pannexin containing channels in the innate and acquired immune response ', Biochimica et Biophysica Acta - Biomembranes , vol. 1860, no. 1, pp. 154-165. (utmb.edu)

We previously provided an overview of the gap junction-independent functions of connexins on cell growth differentiation and tumorigenicity [6]. (liveconscience.com)
The connexins have important roles in controlling cell growth and differentiation and in maintaining tissue homeostasis. (ous-research.no)

We discovered that a small subset of beta connexins (Cx26, Cx30 and Cx32) are directly sensitive to CO 2 -the plasma membrane channels of these connexins open to increases in CO 2 . (warwick.ac.uk)

In this review we provide an updated overview on the current knowledge of gap junction- and hemichannel-independent functions of connexins in particular their effects on tumorigenesis neurogenesis and disease development. (liveconscience.com)
In recent years more studies have focused on the gap junction-and hemichannel-independent roles of connexins. (liveconscience.com)
The Carboxy Terminal Residues 220-283 Are Not Required for Voltage Gating of a Chimeric Connexin 32 Hemichannel. (cuny.edu)
Conformational Changes in a Pore Forming Region Underlie Voltage Dependent Loop-Gating for an Unapposed Connexin Hemichannel. (cuny.edu)

The pH sensitivity depends on the type of connexin composing the gap junction, but the channels generally close at a pH of 6.4-6.2. (wikipedia.org)
In addition to their role as membrane channels, connexins have been shown to interact with intracellular structural and signalling molecules [ 9 ], adding yet another layer of complexity to their function. (biomedcentral.com)
In the current review, we discuss the role of Cx and Panx containing channels in immune activation and the pathogenesis of several infectious diseases. (utmb.edu)
In the inner ear, channels made from connexin 26 are found in a snail-shaped structure called the cochlea . (medlineplus.gov)
New insights into the mechanisms underlying AF have identified promising new approaches, including the modulation of atrium-specific ion channels, connexins and the ryanodine receptor, the prevention of remodelling processes that lead to the arrhythmia as well as specific molecular events involved in arrhythmia generation. (nature.com)
Figure 1: General mechanisms of AF and role of ion channels for AF stabilization. (nature.com)
Bargiello TA, Oh S, Tang Q, Bargiello NK, Dowd TL, Kwon T.Gating of Connexin Channels by transjunctional-voltage: Conformations and models of open and closed states.Biochim Biophys Acta. (cuny.edu)

however, many of their functional roles in mediating tumor growth remain unknown. (frontiersin.org)
Heart relaxation also stands out as an active process, dependent on the energetic output and on specific ion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. (bvsalud.org)

To me, the most novel finding in this study is that we discovered connexin 43 selectively binds to the PIK3CB/p110beta protein, enabling certain glioblastoma cells to gain chemoresistant traits," Sheng said. (eurekalert.org)

The Complex Subtype-Dependent Role of Connexin 43 (GJA1) in Breast Cancer. (123dok.net)

The function of pannexins in bone and cartilage is beginning to be uncovered, but more research is needed to determine the role of pannexins in bone development, adult bone mass and skeletal homeostasis. (biomedcentral.com)
Gap junction is thought to have a crucial role in maintaining tissue homeostasis. (elsevierpure.com)
Connexins and pannexins are key players in the control of cellular communication and thus in the maintenance of tissue homeostasis. (excli.de)
Dr. Dowd investigates the role of the bone protein osteocalcin on glucose homeostasis, insulin sensitivity, secretion, bone properties and bone fracture using osteocalcin knockout mice (KO). (cuny.edu)

Furthermore we discuss the impact of dysregulated connexins on tumorigenesis and disease development. (liveconscience.com)

2016) "Structural studies of N-terminal mutants of Connexin 26 and Connexin 32 using (1)H NMR spectroscopy. (cuny.edu)

However, the complete picture for the role of Cx32 in breast cancer remains to be elusive. (iyte.edu.tr)

Connexin 26 is a member of the connexin protein family. (medlineplus.gov)

It is well established that the role of the tumor microenvironment (TME) in cancer progression and therapeutic resistance is crucial, but many of the underlying mechanisms are still being elucidated. (frontiersin.org)
Ovarian cancer in particular is one of many cancers in which the role of the TME in cancer progression is relatively well-established. (frontiersin.org)
The above findings indicate that DOK5 plays a key role in the invasion, progression, and the metastasis of cancer. (hindawi.com)
Role of estrogen receptor variants in cancer progression? (123dok.net)

1. Anti-Connexin-32 Antibody (#ACC-211), (1:200). (alomone.com)
2. Anti-Connexin-32 Antibody, preincubated with Connexin-32 Blocking Peptide (#BLP-CC211). (alomone.com)

The mixture of conditions in the microenvironment exemplified by hypoxia-induced ovarian cancer TNTs playing a crucial role in tumor growth, as just one example, is a potential avenue of investigation that will uncover their role in relation to other known factors, including EVs. (frontiersin.org)
In previous studies of gliomas, increased levels of the connexin 43 protein suppressed tumor growth. (eurekalert.org)

Peptide (C)EINKLLSEQDGSLK, corresponding to amino acid residues 247-260 of rat Connexin-32 (Accession P08033 ). (alomone.com)

The study aimed to determine whether the exposure to chronic stress and/or performance of gonadectomy might lead to disturbance in the expression of connexin (Cx) 37, 40 and 43 in the spinal cord (SC), as a potential explanation for sex differences in stress-related chronic pain conditions. (mdpi.com)
Here we found that knockdown of connexin expression, and therefore of gap junction expression, disrupted the coordination of the intercellular calcium wave, and resulted in abnormal development. (uib.no)
Nevertheless, the role of DOK5 expression in the prognosis of gastric cancer (GC) remains unclear. (hindawi.com)
Our results clarified the significant role of DOK5 in the prognosis of GC and offer a potential mechanism by which DOK5 expression might monitor tumor immunity-regulation of the infiltration of immune cells in GC. (hindawi.com)

We further show that tissue-nonspecific alkaline phosphatase (TNAP), an ATP-degrading enzyme, plays a key role in mediating the somnogenic effects of ATP released from astrocytes ( n = 5). (jneurosci.org)
this protein plays an important role in the functioning of the cochlea. (cdc.gov)
It is believed that this local regulatory system plays an important role in the complex mechanisms governing the timing of folliculogenesis and whether a follicle becomes dominant or atretic. (glowm.com)
Parking plays a huge role in the visitor/citizen experience within a place. (connexin.co.uk)
The oral flora likely plays a role in recurrent aphthous ulcers (canker sores), and a dysbiosis of the microbiota has been suggested. (medscape.com)
Inflammation plays an important role in the initiation and perpetuation of AF. (bvsalud.org)

In addition, connexin 26 may be involved in the maturation of certain cells in the cochlea. (medlineplus.gov)

In this study, we newly identified the pivotal role of hypothalamic ventrolateral preoptic (VLPO) astrocytes in the sleep regulation, and provide novel insights into the mechanisms underlying the astrocyte-mediated sleep regulation. (jneurosci.org)
This review focuses on the underlying mechanisms of AQP4 related to its dual role in edema formation and elimination. (benthamscience.com)
Recent progress in vascular aging: mechanisms and its role in age-related diseases. (benthamscience.com)

NMR and structural data for Connexin 32 and Connexin 26 N-terminal peptides. (cuny.edu)
Structural Studies of the N-terminus of Connexin 32 Using 1H NMR spectroscopy. (cuny.edu)

In the past, connexin protein names were based on their molecular weight, however the new nomenclature uses sequential numbers based on which form (alpha or beta) of the gap junction is present. (nih.gov)

Connexins are reportedly able to influence cell adhesion migration and cell cycle in a GJIC-independent manner [6-9]. (liveconscience.com)
Additionally GJIC independent involvement of connexin-associated intercellular adhesion has also been presented [7]. (liveconscience.com)
Role of estrogens and their receptors in adhesion and invasiveness of breast cancer cells. (123dok.net)

On the other hand, the protein GAP 43 seems to play an important role in the formation of the microtubules. (sciencedaily.com)
RNA-seq indicated that oxidative phosphorylation played an important role. (bvsalud.org)

Elucidation of the role of extracellular vesicles (EVs) over the past decade has cast a brighter light on this field. (frontiersin.org)

Our current work concentrates on the shear stress-dependent regulation of Cx37 and Cx40 in healthy endothelium and atherosclerotic vessels as well as on the role of connexins in atherosclerosis-derived complications, such as arterial thrombosis and reperfusion injury. (unige.ch)
We therefore examined the role of Nogo-A and NgR1 in the regulation of neurogenesis. (jneurosci.org)

2 Gap junction-independent functions of connexins on tumorigenic cell growth migration and apoptosis Loewenstein and Kanno [11] first established evidence that liver cancer cells were different from normal liver cells in that they lacked intercellular communication. (liveconscience.com)
The present paper reviews the role of connexins and pannexins in liver toxicity and disease. (excli.de)

and CD8 + T cells play a major role as beta cell killers [ 6 , 7 ]. (springer.com)
In addition, as we will see, glia play several key roles required for maintenance of nervous system health. (anti-agingfirewalls.com)

Zebrafish serve as a powerful animal model, allowing researchers to evaluate the effects of connexin 36 on the whole brain in an intact living system during neural hyperactivity. (cureepilepsy.org)
The researchers described the positive effects of inhibiting connexin 43 activityin their2015 study published in Cancer Re search . (eurekalert.org)

However, their role in the immune response and pathological conditions has only recently been explored. (utmb.edu)

Clinical studies show that deficient or abnormal connexins are frequently found in tumor tissues and cell lines such as breast PCI-34051 cancer prostate cancer lung cancer and many other cancers. (liveconscience.com)
As they act both as sensors and effectors in these deleterious events connexins and pannexins could represent a set of novel clinical diagnostic biomarkers and drug targets. (excli.de)

Connexin 26 is found in cells throughout the body, including the inner ear and the skin. (medlineplus.gov)

Here, we review some of the recent advances and studies that highlight the roles of these changes as well as antigen presentation and stress response pathways in beta cells in the onset and propagation of the autoimmune process in type 1 diabetes. (springer.com)
The role of GABARAPL1/GEC1 in autophagic flux and mitochondrial quality control in MDA-MB-436 breast cancer cells. (123dok.net)
To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). (bvsalud.org)

Previously I have written about the roles of glia and microglia in Alzheimer's disease and in spinal cord injury. (anti-agingfirewalls.com)

If the role of cancer heterocellular signaling via TNTs in the TME is proven to be crucial, then disrupting formation and maintenance of TNTs represents a novel therapeutic approach for ovarian and other similarly invasive peritoneal cancers. (frontiersin.org)

Here, we used optogenetic tools to identify the key roles of VLPO astrocytes in sleep promotion. (jneurosci.org)
While this pathway is well-described in the literature, Sheng says they are the first to identify connexin 43's role in activating it. (eurekalert.org)

Here we provide an updated summary on the growing list of channel-independent functions of connexins. (liveconscience.com)

Anatomy6

Organisms3

Chemicals and Drugs9

Analytical, Diagnostic and Therapeutic Techniques and Equipment3

Phenomena and Processes2

Disciplines and Occupations2

Information Science1

Junctions16

Proteins14

Mutations5

Cx436

Hemichannels2

Subunits2

Physiological3

Transmembrane1

Gene3

Molecule2

Intercellular channels1

Neurons2

Genes1

Pannexin1

Differentiation2

Cx261

Hemichannel4

Channels7

Functional2

Selectively1

GJA11

Homeostasis4

Tumorigenesis1

Mutants1

Cx321

Protein family1

Progression4

Antibody2

Tumor growth2

Amino1

Expression4

Plays6

Cochlea1

Mechanisms3

Structural2

Form1

Adhesion3

Important role2

Extracellular1

Regulation2

Liver2

Play2

Effects2

Pathological1

Clinical2

Found1

Cells3

Spinal1

Cancers1

Identify2

Functions1