title: A co-operative regulation of neuronal excitability by UNC-7 innexin and NCA/NALCN leak channel.
abstract: Gap junctions mediate the electrical coupling and intercellular communication between neighboring cells. Some gap junction proteins, namely connexins and pannexins in vertebrates, and innexins in invertebrates, may also function as hemichannels. A conserved NCA/Dmα1U/NALCN family cation leak channel regulates the excitability and activity of vertebrate and invertebrate neurons. In the present study, we describe a genetic and functional interaction between the innexin UNC-7 and the cation leak channel NCA in Caenorhabditis elegans neurons. While the loss of the neuronal NCA channel function leads to a reduced evoked postsynaptic current at neuromuscular junctions, a simultaneous loss of the UNC-7 function restores the evoked response. The expression of UNC-7 in neurons reverts the effect of the unc-7 mutation; moreover, the expression of UNC-7 mutant proteins that are predicted to be unable to form gap junctions also reverts this effect, suggesting that UNC-7 innexin regulates neuronal activity, in part, through gap junction-independent functions. We propose that, in addition to gap junction-mediated functions, UNC-7 innexin may also form hemichannels to regulate C. elegans' neuronal activity cooperatively with the NCA family leak channels.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada M5G 1X5.
authors.forename: Magali
authors.initials: M
authors.lastname: Bouhours
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Po
authors.forename: Shangbang
authors.initials: S
authors.lastname: Gao
authors.forename: Wesley
authors.initials: W
authors.lastname: Hung
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: John
authors.initials: J
authors.lastname: Georgiou
authors.forename: John C
authors.initials: JC
authors.lastname: Roder
authors.forename: Mei
authors.initials: M
authors.lastname: Zhen
mesh_terms: D000448:Aldicarb / Q000494:pharmacology; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D005799:Genes, Dominant / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009928:Organ Specificity / Q000187:drug effects; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D014162:Transfection
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C094444:Unc-7 protein, C elegans; D000448:Aldicarb; D003545:Cysteine