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

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27 Scopus citations

Abstract

Most chemical neurotransmission occurs through Ca(2+)-dependent evoked or spontaneous vesicle exocytosis. In both cases, Ca(2+) sensing is thought to occur shortly before exocytosis. In this paper, we provide evidence that the Ca(2+) dependence of spontaneous vesicle release may partly result from an earlier requirement of Ca(2+) for the assembly of soluble N-ethylmaleimide-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 Ca(2+)-Calmodulin (CaM)-dependent manner. Ca(2+)-CaM regulation of V100 is not required for vesicle acidification. Specific disruption of the Ca(2+)-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 Ca(2+)-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
JournalThe Journal of cell biology
Volume205
Issue number1
DOIs
Publication statusPublished - 2014

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ASJC Scopus subject areas

  • Medicine(all)

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