1.A.24.1.7
Connexin 30 complex (connexin30.2/connexin31.3 (CX30.2/CX31.3)). Also called connexinΥ3/GJC3/GJε1; 279 aas, encoded by the GJB6 (13q12) gene (Cascella et al. 2016)). ATP is released from cells that stably expressed CX30.2 in a medium with low calcium, suggesting a hemichannel-based function. Liang et al. (2011) suggested that it shares functional properties with pannexin hemichannels rather than gap junction channels.  Defects cause nonsyndromic hypoacusia (hearing loss) due to partial loss of channel activity (Su et al. 2012; Su et al. 2013;  Cascella et al. 2016).  Cx30, but not Cx43, hemichannels close upon protein kinase C activation, showing that connexin hemichannels display not only isoform-specific permeability profiles but also isoform-specific regulation by PKC (Alstrom et al. 2015). The W77S mutant has a dominant negative effect on the formation and function of the gap junction and is probably responsible for hearing loss (Wong et al. 2017). Mutations in Cs30 rescue hearing and reveal roles for gap junctions in cochlear amplification (Lukashkina et al. 2017). The cryo-EM structure of the human Cx31.3/GJC3 connexin hemichannel has been solved (Lee et al. 2020). Cx31.3)/GJC3 hemichannels in the presence and absence of calcium ions and with a hearing-loss mutation R15G were solved at 2.3-, 2.5- and 2.6-Å resolutions, respectively. Compared with available structures of GJICh in the open conformation, the Cx31.3 hemichannel shows substantial structural changes of highly conserved regions in the connexin family, including opening of calcium ion-binding tunnels, reorganization of salt-bridge networks, exposure of lipid-binding sites, and collocation of amino-terminal helices at the cytoplasmic entrance. The hemichannel has a pore with a diameter of ~8 Å and selectively transports chloride ions (Lee et al. 2020).