title: A putative cation channel, NCA-1, and a novel protein, UNC-80, transmit neuronal activity in C. elegans.
abstract: Voltage-gated cation channels regulate neuronal excitability through selective ion flux. NALCN, a member of a protein family that is structurally related to the alpha1 subunits of voltage-gated sodium/calcium channels, was recently shown to regulate the resting membrane potentials by mediating sodium leak and the firing of mouse neurons. We identified a role for the Caenorhabditis elegans NALCN homologues NCA-1 and NCA-2 in the propagation of neuronal activity from cell bodies to synapses. Loss of NCA activities leads to reduced synaptic transmission at neuromuscular junctions and frequent halting in locomotion. In vivo calcium imaging experiments further indicate that while calcium influx in the cell bodies of egg-laying motorneurons is unaffected by altered NCA activity, synaptic calcium transients are significantly reduced in nca loss-of-function mutants and increased in nca gain-of-function mutants. NCA-1 localizes along axons and is enriched at nonsynaptic regions. Its localization and function depend on UNC-79, and UNC-80, a novel conserved protein that is also enriched at nonsynaptic regions. We propose that NCA-1 and UNC-80 regulate neuronal activity at least in part by transmitting depolarization signals to synapses in C. elegans neurons.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Yeh
authors.forename: Sharon
authors.initials: S
authors.lastname: Ng
authors.forename: Mi
authors.initials: M
authors.lastname: Zhang
authors.forename: Magali
authors.initials: M
authors.lastname: Bouhours
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Wesley
authors.initials: W
authors.lastname: Hung
authors.forename: Kyota
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Katya
authors.initials: K
authors.lastname: Melnik-Martinez
authors.forename: Michelle
authors.initials: M
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: William R
authors.initials: WR
authors.lastname: Schafer
authors.forename: Mei
authors.initials: M
authors.lastname: Zhen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002412:Cations / Q000378:metabolism; D002478:Cells, Cultured; D002799:Cholinergic Fibers / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009469:Neuromuscular Junction / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics*; D014018:Tissue Distribution; D014162:Transfection; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002412:Cations; D007473:Ion Channels; D009419:Nerve Tissue Proteins; C525140:UNC-80 protein, C elegans; C520111:Unc-79 protein, C elegans; C525141:unc-77 protein, C elegans; D012701:Serotonin; D005680:gamma-Aminobutyric Acid