Presynaptic CaV2 calcium channel traffic requires CALF-1 and the alpha2-delta subunit UNC-36

Presynaptic voltage-gated calcium channels provide calcium for synaptic vesicle exocytosis. We show here that a GFP-tagged alpha1 subunit of the C. elegans CaV2 channel, UNC-2, is localized to presynaptic active zones of sensory and motor neurons. Synaptic localization of CaV2 requires the alpha2-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 alpha2-delta subunit UNC-36 is also required for endoplasmic reticulum exit of UNC-2, but has additional functions. Genetic and cell biological interactions suggest that CALF-1 couples intracellular traffic to functional maturation of CaV2 presynaptic calcium channels.