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.  J. Cell Biol. 205(1): 21--31.

FBrf0224656

Research paper

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.

PMC3987144 (PMC) (EuropePMC)