Connexins, pannexins, innexins: novel roles of “hemi-channels”

摘要: The advent of multicellular organisms, some 800 million years ago, necessitated the development mechanisms for cell-to-cell synchronization and spread signals across increasingly large cell populations [168, 185]. Many structures have evolved to achieve such functions [4, 15]. Among these mechanisms, one which is prominent in both invertebrate vertebrate world, entire phylogenetic scale, involves transmembrane flux cytosolic extracellular molecules 15, 65, 66, 69–71, 121, 128, 129, 147, 154, 163]. These fluxes, turn, are dependent on formation specific channels that all animal classes made by tetra-span integral membrane proteins [65, 163] (Fig. 1). Fig. 1 Innexins, pannexins, connexins form different types gap junctional “hemi-channels.” Invertebrates express many innexins (purple; 25 isoforms C. elegans) may either junction ... Keywords: Gap junctions, Connexons, Pannexons, Innexons, Membrane channels, Ca2+, ATP, Glutamate Three protein families permeable molecules Early electrophysiological electron microscopy studies converged realization domains concentrate intramembrane particles at sites close apposition, were physical substrate communication [59] tissues [139] 1). finding similar drugs (the long-chain alcohols heptanol octanol) conditions (intracellular acidification) inhibited intercellular systems [58, 85] was taken as further support junctions had a structure function. Still, size particles, their partition into P- E-fracture faces membrane, width space delineated two interacting membranes, suggested making from those [96]. differences functional consequences, most elegantly demonstrated co-culturing lines species. In experiments, heterotypic coupling shown between insect cells, well whereas virtually no observed cells phylogenetically distant species [48]. There longer any question various combinations connexin [66, 69–71]. 20–21 this family rodents man differ size, but share topography. Thus, feature four connected loops, each comprising three highly conserved Cys residues, cytoplasmic loop, N C termini cytosol 2). difference essentially due length loop and/or terminus [39, 64, 109]. Current nomenclature (Table 1) designates nCxZ, where n (e.g., h, m, r human, mouse, rat, respectively), Z predicted molecular weight, kDa. genes encoding named according subgroups, order discovery Gjb1 encodes Cx32, Gjb2 Cx26, Gja1 Cx43, etc). Fig. 2 Membrane topography forming All innexins, ortholog nonhomologous ... Table 1 The human connexins Attempts identify initially revealed Ogre, Passover, Uncoordinated, Shaking B Drosophila Caenorhabditis (hence original OPUS acronym name proteins) with primary sequence homology [128, 195]. Since time, more than other revealing significant similarities been identified elegans, it clear forms expressed [75, 195] Collectively, stress distribution role, analogous connexins, Strikingly, also 2), even though sets amino acid Notably, display within only carry residues. curious retrospect hydra reported be blocked an antibody prepared against Cx32 [53], antibodies detected connexin-like anemone [112] marine invertebrates [5], isolated hepatopancreas crayfish lobster rat liver [51]. Table 2 A present view growing innexins Sequencing mammalian genomes has third code showing about 20% similarity [121, On basis, thought represent homologs termed pannexins 3) encompass members 154]. Like N- C-terminal cytoplasm, domains, spanning segments contrast contain residues Furthermore, marked consensus sequences glycosylation [13, 14, 125] Pnx1 (Pnx1), studied form, widespread and, tissues, largely overlaps [17, 8]. While least phenotypes resulting loss not compensated pannexin changes [136, 146], suggesting function families, cases, effects transfection mimicked implicating comparable/overlapping role [93]. Table 3 The pannexins Connexins regions membrane Expression deletion variety established hexamers, connexons, reduced 2–3 nm wide. At sites, connexons align with, strongly bind adjacent cell, establishing continuous hydrophilic pathway exchange multiple [64, 155]. importance electrical metabolic striking tissue-specific can experimentally induced after overexpression or knock-out individual isoforms, knock-in replacement isoform another [92, 192]. It stressed identification number diseases undoubtedly linked mutations [43, 57, 90, 94, 127, 143]. A altered amounts [21, 108, 153]. Similarly, oligomerize innexons cluster Functional expression paired Xenopus oocytes several, formed [8, 95, 166], innexin give rise expected lack junction-mediated [10, 25, 27, 37, 179]. fact, basis dysfunctional gene first identified. In contrast, spite initial report [18], pannexons appear unable sizable under [76, 146, This likely loops 125], which, mentioned above, innexins. forced increased conductance current carrying ions way accounted [13].