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Beschreibung

Gap junction alpha-1 protein (UniProt: P17302, also known as Connexin-43, Cx43, Gap junction 43 kDa heart protein) is encoded by the GJA1 (also known as GJAL) gene (Gene ID: 2697) in human. Cx43 is a member of the gap junction family, which is composed of intercellular channels allowing direct cell-to-cell communication between neighboring cells via the exchange of small ions and metabolites. It is a multi-pass membrane protein with three cytoplasmic domains, four transmembrane domains, and two extracellular domains. It is one of the most widely studied gap junction proteins that regulates N-cadherin expression during collective cell migration. It also acts as a negative regulator of bladder capacity by enhancing intercellular electrical and chemical transmission and thereby exsensitizing bladder muscles to cholinergic neural stimuli and causing them to contract. It is also expressed in gap junctions of the cardiac ventricle and plays an essential role in gap junction communication in the ventricles. Cx43 can be phosphorylated at multiple sites and phosphorylation is shown to regulate the kinetics of its trafficking, assembly, gating and turnover in a cell-cycle-stage specific manner. Cx43 is phosphorylated at Ser-368 by PKCg (PRKCG) and this phosphorylation is reported to induce disassembly of gap junction plaques and inhibition of gap junction activity and triggers its internalization into small vesicles leading to proteasome-mediated degradation. (Ref.: Solan, JL., and Lampe, PD. (2020). Biomolecules. 10(12), 1596, Kotini, M., et al. (2018). Nature Commun. 9, article 3846).