Presynaptic CaV2 calcium channel traffic requires CALF-1 and the alpha(2)delta subunit UNC-36.
Presynaptic voltage-gated calcium channels provide calcium for synaptic vesicle exocytosis. We show here that a green fluorescent protein-tagged alpha(1) subunit of the Caenorhabditis elegans CaV2 channel, UNC-2, is localized to presynaptic active zones of sensory and motor neurons. Synaptic localization of CaV2 requires the alpha(2)delta subunit UNC-36 and CALF-1 (Calcium Channel Localization Factor-1), a neuronal transmembrane protein that localizes to the endoplasmic reticulum. In calf-1 mutants, UNC-2 is retained in the endoplasmic reticulum, but other active-zone components and synaptic vesicles are delivered to synapses. Acute induction of calf-1 mobilizes preexisting UNC-2 for delivery to synapses, consistent with a direct trafficking role. The alpha(2)delta subunit UNC-36 is likewise required for exit of UNC-2 from endoplasmic reticulum but has additional functions. Genetic and cell biological interactions suggest that CALF-1 couples intracellular traffic to functional maturation of CaV2 presynaptic calcium channels.
Saheki
Yasunori
Y
Howard Hughes Medical Institute and Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, New York, USA.
Bargmann
Cornelia I
CI
D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D016009:Chi-Square Distribution; D002874:Chromosome Mapping / Q000379:methods; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D005089:Exocytosis; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007422:Intestines / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D013550:Swimming / Q000502:physiology; D013569:Synapses / Q000502:physiology; D025262:Vacuolar Proton-Translocating ATPases / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; C544134:calcium channel cocalization factor-1, C elegans; C093204:unc-2 protein, C elegans; D049452:Green Fluorescent Proteins; D025262:Vacuolar Proton-Translocating ATPases; C506981:unc-32 protein, C elegans; D002118:Calcium