Cx43 | Connexin 43
Family:
Connexins
Topology:
Connexins form so-called gap junctions. 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. Connexins contain four highly ordered transmembrane segments (TMSs). The connexin gene family is diverse, with twenty-one identified members in the sequenced human genome.
Function:
Connexins (Cx) are structurally related transmembrane proteins that assemble to form vertebrate gap junctions. 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. By forming a syncytium between cell, connexins provide electric coupling and direct cell-cell communication of small molecules.
Cx43 Background Information
Overview:
Gap junction alpha-1 protein (GJA1), also known as connexin 43 (Cx43), is a component of gap junctions, which allow intercellular communication between cells to regulate cell death, proliferation, and differentiation. As a result of its function, connexin-43 is implicated in many biological processes, including muscle contraction, embryonic development, inflammation, spermatogenesis, bladder contraction regulation.
Data Sheet:
Gene:
GJA1
Human Protein:
UniProt P17302
Tissue:
CX43 the most ubiquitously expressed connexin and is detected in many different cell types. It is the major gap junction component in the heart, in the CNS CX43 is localized in glial cells (astrocytes) and endothelial cells. CX43 is expressed in many immune cells, such as eosinophils and T cells, where its gap junction function promotes the maturation and activation of these cells
Function/ Application:
Acts via forming gap junctions by enhancing intercellular electrical and chemical transmission (passive diffusion of low molecular weight materials up to 1 kDa, including nutrients, metabolites (glucose), ions and second messengers (IP3, cAMP)). It is important for the synchronized contraction of the heart. Cx43 has furthermore channel-independent functions: In the cytoplasm, the protein regulates the microtubule network and, by extension, cell migration and polarity.
Pathology:
Oculodentodigital dysplasia (ODDD), Syndactyly 3 (SDTY3), Hypoplastic left heart syndrome 1 (HLHS1), Hallermann-Streiff syndrome (HSS), Atrioventricular septal defect 3 (AVSD3), Craniometaphyseal dysplasia (CMDR), Erythrokeratodermia variabilis et progressiva 3 (EKVP3) and Palmoplantar keratoderma and congenital alopecia 1 (PPKCA1) are diseases which may be caused by mutations of GJA1
Interaction:
Interacts with further connexins (Cx37,Cx40,Cx45), ZO-1, MAPK7, Caveolin, CSNK1D, PTPmu, SRC, UBQLN4, SGSM3, CNST, RIC1/CIP150, CSNK1D, NOV, TMEM65.
Modulator:
Flufenamic acid, carbenoxolone, octanol, extracellular Ca2+
Assays:
& 
Bilayer recordings on Port-a-Patch and Orbit mini
& 
Contractility recordings on CardioExcyte 96 and FLEXcyte 96
Reviews and Links
Recommended Reviews:
- Roberto Bruzzone (2001) Learning the language of cell-cell communication through connexin channels. Genome Biology 2(11):reports4027.1–4027.5
- Ryo Yamasaki (2018) Connexins in health and disease. Clinical and Experimental Neuroimmunology 9(1): 30–36
Transporter classification database:
UniProt:
IUPHAR/PBS:
Publications
2020 - Metformin therapy confers cardioprotection against the remodeling of gap junction in tachycardia-induced atrial fibrillation dog model
CardioExcyte 96 publication in Frontiers in Life Sciences (2020)
Authors:
Li J., Li B., Bai F., Ma Y., Liu N., Liu Y., Wang Y., Liu Q.
2020 - Interferon-γ and high glucose-induced opening of Cx43 hemichannels causes endothelial cell dysfunction and damage
Port-a-Patch publication in Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (2020)
Authors:
Sáez J.C., Contreras-Duarte S., Labra V.C., Santibañez C.A., Mellado L.A., Inostroza C.A., Alvear T.F., Retamal M.A., Velarde V., Orellana J.A..
2020 - Cryo-EM structure of human Cx31.3/GJC3 connexin hemichannel
Orbit mini publication in Science Advances (2020)
Authors:
Lee H.J., Jeong H., Hyun J., Ryu B., Park K., Lim H.H., Yoo J., Woo J.S.
2012 - Green Fluorescent Protein Changes the Conductance of Connexin 43 (Cx43) Hemichannels Reconstituted in Planar Lipid Bilayer
Port-a-Patch and 
Vesicle Prep Pro publication in The Journal of Biological Chemistry (2012)
Authors:
Carnarius C., Kreir M., Krick M., Methfessel C., Moehrle V., Valerius O., Brüggemann A., Steinem C., Fertig N.