A Putative Cation Channel, NCA-1, and a Novel Protein, UNC-80, Transmit Neuronal Activity in C. elegans |
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| Authors: | Edward Yeh Edward Yeh Edward Yeh Edward Yeh Edward Yeh Edward Yeh Edward Yeh Edward Yeh Edward Yeh Edward Yeh |
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| Affiliation: | 1, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada;2, Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada;3, Division of Biology, University of California San Diego, San Diego, California, United States of America;4, Department of Neuroscience, Centre for Addiction and Mental Health, Clarke Division, University of Toronto, Toronto, Ontario, Canada;5, Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom;Cambridge University, United Kingdom |
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| 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 α1 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. |
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