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

J Cell Biol. 2014 Apr 14;205(1):21-31. doi: 10.1083/jcb.201312109.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calmodulin / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / enzymology*
  • Drosophila melanogaster / genetics
  • Electric Stimulation
  • Hydrogen-Ion Concentration
  • Lysosomes / enzymology
  • Multiprotein Complexes
  • Neuromuscular Junction / enzymology*
  • Protein Binding
  • Protein Subunits
  • Qa-SNARE Proteins / genetics
  • Qa-SNARE Proteins / metabolism*
  • Synaptic Transmission*
  • Synaptic Vesicles / enzymology*
  • Time Factors
  • Vacuolar Proton-Translocating ATPases / genetics
  • Vacuolar Proton-Translocating ATPases / metabolism*


  • Calmodulin
  • Drosophila Proteins
  • Multiprotein Complexes
  • Protein Subunits
  • Qa-SNARE Proteins
  • syntaxin, Drosophila
  • Vacuolar Proton-Translocating ATPases
  • Vha100-1 protein, Drosophila
  • Calcium