title: The V-ATPase membrane domain is a sensor of granular pH that controls the exocytotic machinery.
abstract: Several studies have suggested that the V0 domain of the vacuolar-type H(+)-adenosine triphosphatase (V-ATPase) is directly implicated in secretory vesicle exocytosis through a role in membrane fusion. We report in this paper that there was a rapid decrease in neurotransmitter release after acute photoinactivation of the V0 a1-I subunit in neuronal pairs. Likewise, inactivation of the V0 a1-I subunit in chromaffin cells resulted in a decreased frequency and prolonged kinetics of amperometric spikes induced by depolarization, with shortening of the fusion pore open time. Dissipation of the granular pH gradient was associated with an inhibition of exocytosis and correlated with the V1-V0 association status in secretory granules. We thus conclude that V0 serves as a sensor of intragranular pH that controls exocytosis and synaptic transmission via the reversible dissociation of V1 at acidic pH. Hence, the V-ATPase membrane domain would allow the exocytotic machinery to discriminate fully loaded and acidified vesicles from vesicles undergoing neurotransmitter reloading.
authors.affiliation: Centre de Neurosciences Paris-Sud, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8195 and Université Paris-Sud, F-91405 Orsay, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Poëa-Guyon
authors.forename: Mohamed Raafet
authors.initials: MR
authors.lastname: Ammar
authors.forename: Marie
authors.initials: M
authors.lastname: Erard
authors.forename: Muriel
authors.initials: M
authors.lastname: Amar
authors.forename: Alexandre W
authors.initials: AW
authors.lastname: Moreau
authors.forename: Philippe
authors.initials: P
authors.lastname: Fossier
authors.forename: Vincent
authors.initials: V
authors.lastname: Gleize
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vitale
authors.forename: Nicolas
authors.initials: N
authors.lastname: Morel
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D019439:Chromaffin Cells / Q000201:enzymology / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects / Q000528:radiation effects; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008027:Light; D008561:Membrane Fusion; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism / Q000528:radiation effects; D016716:PC12 Cells; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism / Q000528:radiation effects; D055366:Synaptic Potentials; D009435:Synaptic Transmission / Q000187:drug effects / Q000528:radiation effects; D013572:Synaptic Vesicles / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism / Q000528:radiation effects; D014162:Transfection; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D011993:Recombinant Fusion Proteins; D025262:Vacuolar Proton-Translocating ATPases; C569187:vacuolar ATPase V0 subunit A1, rat