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

Jérôme Di Giovanni, 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

    Research outputpeer-review

    76 Scopus citations


    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 Ca2+-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.

    Original languageEnglish
    Pages (from-to)268-279
    Number of pages12
    Issue number2
    StatePublished - Jul 2010

    ASJC Scopus subject areas

    • General Neuroscience

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