Calcium/Calmodulin regulates SNARE assembly and spontaneous neurotransmitter release via v-ATPase subunit V0a1

Wang, D., Epstein, D., Khalaf, O., Srinivasan, S., Williamson, W.R., Fayyazuddin, A., Quiocho, F.A., and Hiesinger, P.R.— 2014

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 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 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.

TitleCalcium/Calmodulin regulates SNARE assembly and spontaneous neurotransmitter release via v-ATPase subunit V0a1
AuthorWang, D., Epstein, D., Khalaf, O., Srinivasan, S., Williamson, W.R., Fayyazuddin, A., Quiocho, F.A., and Hiesinger, P.R.
PublisherRockefeller University Press
Date20140414
Identifierdoi: 10.1083/jcb.201312109
Source(s)
Relation
Appeared InJ. Cell. Biol. 205(1):21-31
Languageeng
TypeText
Rights© 2014 Wang et al. Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license)