Presynaptic CaV2 calcium channel traffic requires CALF-1 and the α2δ subunit UNC-36

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Abstract
In C. elegans, the unc-2 gene encodes the pore-forming subunit of a voltage-gated Ca2+ channel (CaV2) involved in neurotransmitter release. Here, the authors identify a protein, CALF-1, that regulates the presynaptic trafficking of UNC-2. The α2δ subunit UNC-36 is also required for ER exit and synaptic localization of UNC-2. Presynaptic voltage-gated calcium channels provide calcium for synaptic vesicle exocytosis. We show here that a green fluorescent protein–tagged α1 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 α2δ 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 α2δ 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.

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