Presynaptic CaV2 calcium channel traffic requires CALF-1 and the alpha(2)delta subunit UNC-36

Nat Neurosci. 2009 Oct;12(10):1257-65. doi: 10.1038/nn.2383. Epub 2009 Aug 30.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Behavior, Animal
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology*
  • Calcium / metabolism
  • Calcium Channels / metabolism*
  • Chi-Square Distribution
  • Chromosome Mapping / methods
  • Endoplasmic Reticulum / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / ultrastructure
  • Exocytosis
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Green Fluorescent Proteins / genetics
  • Intestines / cytology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Presynaptic Terminals / metabolism*
  • Protein Subunits / metabolism
  • Protein Transport / genetics
  • Protein Transport / physiology
  • Swimming / physiology
  • Synapses / physiology
  • Vacuolar Proton-Translocating ATPases / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Calcium Channels
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Protein Subunits
  • calcium channel cocalization factor-1, C elegans
  • unc-2 protein, C elegans
  • Green Fluorescent Proteins
  • Vacuolar Proton-Translocating ATPases
  • unc-32 protein, C elegans
  • Calcium