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Connexins: a myriad of functions extending beyond assembly of gap junction channels

Journal Article · · Cell Communication and Signaling
 [1];  [2];  [3];  [4]
  1. American Univ. of Beirut (Lebanon). Faculty of Arts and Sciences, Dept. of Biology; Albert Einstein College of Medicine, Bronx, NY (United States). Dept. of Molecular Pharmacology; DOE/OSTI
  2. American Univ. of Beirut (Lebanon). Faculty of Arts and Sciences, Dept. of Biology; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Division of Life Sciences
  3. American Univ. of Beirut (Lebanon). Faculty of Medicine, Dept. of Human Morphology
  4. American Univ. of Beirut (Lebanon). Faculty of Arts and Sciences, Dept. of Biology
+ Show Author Affiliations
Connexins constitute a large family of trans-membrane proteins that allow intercellular communication and the transfer of ions and small signaling molecules between cells. Recent studies have revealed complex translational and post-translational mechanisms that regulate connexin synthesis, maturation, membrane transport and degradation that in turn modulate gap junction intercellular communication. With the growing myriad of connexin interacting proteins, including cytoskeletal elements, junctional proteins, and enzymes, gap junctions are now perceived, not only as channels between neighboring cells, but as signaling complexes that regulate cell function and transformation. Connexins have also been shown to form functional hemichannels and have roles altogether independent of channel functions, where they exert their effects on proliferation and other aspects of life and death of the cell through mostly-undefined mechanisms. This review provides an updated overview of current knowledge of connexins and their interacting proteins, and it describes connexin modulation in disease and tumorigenesis.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
Lebanese National Council for Scientific Research; USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1626579
Journal Information:
Cell Communication and Signaling, Journal Name: Cell Communication and Signaling Journal Issue: 1 Vol. 7; ISSN 1478-811X
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

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  • Paznekas, William A.; Boyadjiev, Simeon A.; Shapiro, Robert E.
  • The American Journal of Human Genetics, Vol. 72, Issue 2 https://doi.org/10.1086/346090
journal February 2003
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The Coiled-coil Domain of Occludin Can Act to Organize Structural and Functional Elements of the Epithelial Tight Junction journal September 2000
c-Src Regulates the Interaction between Connexin-43 and ZO-1 in Cardiac Myocytes journal January 2001
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Connexin45 Interacts with Zonula Occludens-1 and Connexin43 in Osteoblastic Cells journal June 2001
A Self-restricted CD38-connexin 43 Cross-talk Affects NAD+ and Cyclic ADP-ribose Metabolism and Regulates Intracellular Calcium in 3T3 Fibroblasts journal December 2001
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Retroviral Delivery of Connexin Genes to Human Breast Tumor Cells Inhibits in Vivo Tumor Growth by a Mechanism That Is Independent of Significant Gap Junctional Intercellular Communication journal August 2002
Impaired Trafficking of Connexins in Androgen-independent Human Prostate Cancer Cell Lines and Its Mitigation by α-Catenin journal December 2002
Gap Junctional Communication Modulates Gene Transcription by Altering the Recruitment of Sp1 and Sp3 to Connexin-response Elements in Osteoblast Promoters journal July 2003
Lysosomal and Proteasomal Degradation Play Distinct Roles in the Life Cycle of Cx43 in Gap Junctional Intercellular Communication-deficient and -competent Breast Tumor Cells journal August 2003
The Gap Junction-independent Tumor-suppressing Effect of Connexin 43 journal November 2003
Connexin43 Associated with an N-cadherin-containing Multiprotein Complex Is Required for Gap Junction Formation in NIH3T3 Cells journal May 2005
Connexin 43 Interacts with Zona Occludens-1 and -2 Proteins in a Cell Cycle Stage-specific Manner journal August 2005
Enhanced Neurite Outgrowth in PC12 Cells Mediated by Connexin Hemichannels and ATP journal July 2006
Characterization of the pH-dependent Interaction between the Gap Junction Protein Connexin43 Carboxyl Terminus and Cytoplasmic Loop Domains journal December 2006
The Structural Context of Disease-causing Mutations in Gap Junctions journal September 2006
An Update on Connexin Genes and their Nomenclature in Mouse and Man journal January 2003
Association of Connexin43 with a Receptor Protein Tyrosine Phosphatase journal January 2003
Identification of Connexin-43 Interacting Proteins journal January 2003
Functioning of Cx43 Hemichannels Demonstrated by Single Channel Properties journal January 2003
A Potential Role for Cx43-Hemichannels in Staurosporin-Induced Apoptosis journal January 2003
Regulation of connexin 43-mediated gap junctional intercellular communication by Ca2+ in mouse epidermal cells is controlled by E-cadherin. journal August 1991
Biochemical analysis of connexin43 intracellular transport, phosphorylation, and assembly into gap junctional plaques. journal December 1991
Cytoplasmic dye transfer between metastatic tumor cells and vascular endothelium. journal December 1991
Transcriptional downregulation of gap-junction proteins blocks junctional communication in human mammary tumor cell lines. journal September 1992
Inhibition of gap junction and adherens junction assembly by connexin and A-CAM antibodies. journal October 1992
Binding of ribosomes to the rough endoplasmic reticulum mediated by the Sec61p-complex. journal August 1994
Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells. journal May 1995
Properties and regulation of gap junctional hemichannels in the plasma membranes of cultured cells. journal August 1996
Connexin46 Is Retained as Monomers in a trans-Golgi Compartment of Osteoblastic Cells journal May 1997
Acute loss of Cell–Cell Communication Caused by G Protein–coupled Receptors: A Critical Role for c-Src journal March 1998
Transplacental Uptake of Glucose Is Decreased in Embryonic Lethal Connexin26-deficient Mice journal March 1998
Regulation of Connexin Hemichannels by Monovalent Cations journal December 2005
Connexin46 Mutations in Autosomal Dominant Congenital Cataract journal May 1999
Connexin-Caused Genetic Diseases and Corresponding Mouse Models journal February 2009
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Gap Junctions Regulate Extracellular Signal-regulated Kinase Signaling to Affect Gene Transcription journal January 2005
Mechanical Strain Opens Connexin 43 Hemichannels in Osteocytes: A Novel Mechanism for the Release of Prostaglandin journal July 2005
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Augmentation of differentiation and gap junction function by kaempferol in partially differentiated colon cancer cells journal September 2004
Cx26 inhibits breast MDA-MB-435 cell tumorigenic properties by a gap junctional intercellular communication-independent mechanism journal August 2006
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Localization of regulatory protein binding sites in the proximal region of human myometrial connexin 43 gene journal August 1999
MIR-206 regulates connexin43 expression during skeletal muscle development journal November 2006
Pharmacological modification of gap junction coupling by an antiarrhythmic peptide via protein kinase C activation journal May 2002
Isoelectric points and post‐translational modifications of connexin26 and connexin32 journal April 2006
The role of gap junctions in health and disease journal January 2005
Connexins and Impulse Propagation in the Mouse Heart journal December 1999
Characterization of Targeted Connexin32-Deficient Mice: A Model for the Human Charcot-Marie-Tooth (X-Type) Inherited Disease journal October 1999
Connexin-specific cell-to-cell transfer of short interfering RNA by gap junctions: Oligonucleotide and siRNA transfer through gap junctions journal October 2005
Ischemia Opens Neuronal Gap Junction Hemichannels journal May 2006
Integrin Signaling journal August 1999
Phosphorylation of connexin43 gap junction protein in uninfected and Rous sarcoma virus-transformed mammalian fibroblasts. journal April 1990
Structure-activity relations of the cardiac gap junction channel journal February 1990
Heterotypic gap junction channel formation between heteromeric and homomeric Cx40 and Cx43 connexons journal November 2001
Endogenous protein phosphatase 1 runs down gap junctional communication of rat ventricular myocytes journal November 2001
Heterocellular gap junctional communication between alveolar epithelial cells journal June 2001
Libri / Varia journal January 1968
Connexin 43 Downregulation and Dephosphorylation in Nonischemic Heart Failure Is Associated With Enhanced Colocalized Protein Phosphatase Type 2A journal January 2005
Impairment of Diazoxide-Induced Formation of Reactive Oxygen Species and Loss of Cardioprotection in Connexin 43 Deficient Mice journal September 2005
Translocation of Connexin 43 to the Inner Mitochondrial Membrane of Cardiomyocytes Through the Heat Shock Protein 90–Dependent TOM Pathway and Its Importance for Cardioprotection journal July 2006
Relative Contributions of Connexins 40 and 43 to Atrial Impulse Propagation in Synthetic Strands of Neonatal and Fetal Murine Cardiomyocytes journal November 2006
The ε Subtype of Protein Kinase C Is Required for Cardiomyocyte Connexin-43 Phosphorylation journal February 2000
Increased Association of ZO-1 With Connexin43 During Remodeling of Cardiac Gap Junctions journal February 2002
The Carboxyl Terminal Domain Regulates the Unitary Conductance and Voltage Dependence of Connexin40 Gap Junction Channels journal April 2001
Stimulation of Lens Cell Differentiation by Gap Junction Protein Connexin 45.6 journal May 2003
Posttranslational Modifications in Lens Fiber Connexins Identified by Off-Line-HPLC MALDI-Quadrupole Time-of-Flight Mass Spectrometry journal April 2008
Wnt-1 regulation of connexin43 in cardiac myocytes journal January 2000
Human T-cell lymphotropic virus type 1–transformed cells induce angiogenesis and establish functional gap junctions with endothelial cells journal May 2002
Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture journal May 2005
Role of Connexin 43 in Sertoli Cells of Testis journal December 2007
Identification and developmental regulation of cadherin messenger ribonucleic acids in the rat testis. journal July 1992
New connexin32 mutations associated with X-linked Charcot-Marie-Tooth disease journal October 1995
A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia journal October 2005
Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells journal September 2006
ECM-induced gap junctional communication enhances mammary epithelial cell differentiation journal September 2003
Selective assembly of connexin37 into heterocellular gap junctions at the oocyte/granulosa cell interface journal June 2004
ZO-1 alters the plasma membrane localization and function of Cx43 in osteoblastic cells journal May 2005
Oculodentodigital dysplasia connexin43 mutations result in non-functional connexin hemichannels and gap junctions in C6 glioma cells journal February 2006
Dynamics of connexins, E-cadherin and alpha-catenin on cell membranes during gap junction formation journal February 1997
Role of Gap Junctional Intercellular Communication (GJIC) through p38 and ERK1/2 Pathway in the Differentiation of Rat Neuronal Stem Cells journal January 2005
Expression of MAP Kinases and Connexins in the Differentiation of Rat Mammary Epithelial Cells journal January 2006
ODDD-Linked Cx43 Mutants Reduce Endogenous Cx43 Expression and Function in Osteoblasts and Inhibit Late Stage Differentiation journal February 2008
Structural and Functional Diversity of Connexin Genes in the Mouse and Human Genome journal January 2002
Evolutionary selection pressure and family relationships among connexin genes journal March 2007
Functional Coupling between Neurons and Glia journal June 2000
Calmodulin Kinase Pathway Mediates the K + -Induced Increase in Gap Junctional Communication between Mouse Spinal Cord Astrocytes journal September 2001
Role of gap junctions during early embryo development journal February 2005
Identification of a protein kinase activity that phosphorylates connexin43 in a pH-dependent manner journal April 2000
The function of connexin 43 on the differentiation of rat bone marrow cells in culture journal January 2006
Connexin45 Interacts with Zonula Occludens-1 in Osteoblastic Cells journal January 2001
Connexin-43 Interactions with ZO-1 and α- and β-tubulin journal January 2001
v-Src-Mediated Phosphorylation of Connexin43 on Tyrosine Disrupts Gap Junctional Communication in Mammalian Cells journal January 2001
N-Cadherin and Cx43α1 Gap Junctions Modulates Mouse Neural Crest Cell Motility via Distinct Pathways journal January 2001
Proliferation and Polarity in Breast Cancer: Untying the Gordian Knot journal March 2005

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Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy journal January 2013
Distinctive actions of connexin 46 and connexin 50 in anterior pituitary folliculostellate cells journal July 2017
Cell surface membrane proteins as personalized biomarkers: where we stand and where we are headed journal October 2013
Impaired membrane targeting and aberrant cellular localization of human Cx26 mutants associated with inherited recessive hearing loss journal August 2010
Tight Junction Proteins and Signaling Pathways in Cancer and Inflammation: A Functional Crosstalk journal January 2019
A Cell Junctional Protein Network Associated with Connexin-26 journal August 2018
Fenofibrate Reduces the Asthma-Related Fibroblast-To-Myofibroblast Transition by TGF-Β/Smad2/3 Signaling Attenuation and Connexin 43-Dependent Phenotype Destabilization journal August 2018
The putative role of lutein and zeaxanthin as protective agents against age-related macular degeneration: promise of molecular genetics for guiding mechanistic and translational research in the field journal October 2012

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59 BASIC BIOLOGICAL SCIENCES
Cell Biology