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

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

Edité par CCSD ; Elsevier -

International audience. 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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