Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Behavior, Animal
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Caenorhabditis elegans
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism
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Caenorhabditis elegans Proteins / physiology*
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Calcium / metabolism
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Calcium Channels / metabolism*
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Chi-Square Distribution
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Chromosome Mapping / methods
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Endoplasmic Reticulum / metabolism
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Epithelial Cells / metabolism
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Epithelial Cells / ultrastructure
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Exocytosis
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Gene Expression Regulation / genetics
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Gene Expression Regulation / physiology*
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Green Fluorescent Proteins / genetics
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Intestines / cytology
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Membrane Proteins / physiology*
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Mutation
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neurons / cytology
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Neurons / metabolism
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Neurons / ultrastructure
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Presynaptic Terminals / metabolism*
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Protein Subunits / metabolism
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Protein Transport / genetics
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Protein Transport / physiology
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Swimming / physiology
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Synapses / physiology
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Vacuolar Proton-Translocating ATPases / physiology*
Substances
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Caenorhabditis elegans Proteins
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Calcium Channels
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Membrane Proteins
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Nerve Tissue Proteins
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Protein Subunits
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calcium channel cocalization factor-1, C elegans
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unc-2 protein, C elegans
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Green Fluorescent Proteins
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Vacuolar Proton-Translocating ATPases
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unc-32 protein, C elegans
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Calcium