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. 2010 Jul 29;67(2):268-79.
doi: 10.1016/j.neuron.2010.06.024.

V-ATPase membrane sector associates with synaptobrevin to modulate neurotransmitter release

Jérôme Di Giovanni  1 , Sami Boudkkazi, Sumiko Mochida, Andrzej Bialowas, Nada Samari, Christian Lévêque, Fahamoe Youssouf, Aline Brechet, Cécile Iborra, Yves Maulet, Nicole Moutot, Dominique Debanne, Michael Seagar, Oussama El Far
Affiliations
Free article

V-ATPase membrane sector associates with synaptobrevin to modulate neurotransmitter release

Jérôme Di Giovanni et al. Neuron. .
Free article

Abstract

Acidification of synaptic vesicles by the vacuolar proton ATPase is essential for loading with neurotransmitter. Debated findings have suggested that V-ATPase membrane domain (V0) also contributes to Ca(2+)-dependent transmitter release via a direct role in vesicle membrane fusion, but the underlying mechanisms remain obscure. We now report a direct interaction between V0 c-subunit and the v-SNARE synaptobrevin, constituting a molecular link between the V-ATPase and SNARE-mediated fusion. Interaction domains were mapped to the membrane-proximal domain of VAMP2 and the cytosolic 3.4 loop of c-subunit. Acute perturbation of this interaction with c-subunit 3.4 loop peptides did not affect synaptic vesicle proton pump activity, but induced a substantial decrease in neurotransmitter release probability, inhibiting glutamatergic as well as cholinergic transmission in cortical slices and cultured sympathetic neurons, respectively. Thus, V-ATPase may ensure two independent functions: proton transport by a fully assembled V-ATPase and a role in SNARE-dependent exocytosis by the V0 sector.

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