Ca2+-Calmodulin regulates SNARE assembly and spontaneous neurotransmitter release via v-ATPase subunit V0a1

Dong Wang, Daniel Epstein, Ossama Khalaf, Sankaranarayanan Srinivasan, W. Ryan Williamson, Amir Fayyazuddin, Florante A. Quiocho, P. Robin Hiesinger

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Most chemical neurotransmission occurs through Ca2+-dependent evoked or spontaneous vesicle exocytosis. In both cases, Ca2+ sensing is thought to occur shortly before exocytosis. In this paper, we provide evidence that the Ca2+ dependence of spontaneous vesicle release may partly result from an earlier requirement of Ca2+ for the assembly of soluble Nethylmaleimide- sensitive fusion attachment protein receptor (SNARE) complexes. We show that the neuronal vacuolar-type H+-adenosine triphosphatase V0 subunit a1 (V100) can regulate the formation of SNARE complexes in a Ca2+-Calmodulin (CaM)-dependent manner. Ca2+-CaM regulation of V100 is not required for vesicle acidification. Specific disruption of the Ca2+-dependent regulation of V100 by CaM led to a >90% loss of spontaneous release but only had a mild effect on evoked release at Drosophila melanogaster embryo neuromuscular junctions. Our data suggest that Ca2+-CaM regulation of V100 may control SNARE complex assembly for a subset of synaptic vesicles that sustain spontaneous release.

Original languageEnglish (US)
Pages (from-to)21-31
Number of pages11
JournalJournal of Cell Biology
Volume205
Issue number1
DOIs
StatePublished - Apr 2014

ASJC Scopus subject areas

  • Cell Biology

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    Wang, D., Epstein, D., Khalaf, O., Srinivasan, S., Williamson, W. R., Fayyazuddin, A., Quiocho, F. A., & Hiesinger, P. R. (2014). Ca2+-Calmodulin regulates SNARE assembly and spontaneous neurotransmitter release via v-ATPase subunit V0a1. Journal of Cell Biology, 205(1), 21-31. https://doi.org/10.1083/jcb.201312109