title: The membrane domain of vacuolar H(+)ATPase: a crucial player in neurotransmitter exocytotic release.
abstract: V-ATPases are multimeric enzymes made of two sectors, a V1 catalytic domain and a V0 membrane domain. They accumulate protons in various intracellular organelles. Acidification of synaptic vesicles by V-ATPase energizes the accumulation of neurotransmitters in these storage organelles and is therefore required for efficient synaptic transmission. In addition to this well-accepted role, functional studies have unraveled additional hidden roles of V0 in neurotransmitter exocytosis that are independent of the transport of protons. V0 interacts with SNAREs and calmodulin, and perturbing these interactions affects neurotransmitter release. Here, we discuss these data in relation with previous results obtained in reconstituted membranes and on yeast vacuole fusion. We propose that V0 could be a sensor of intra-vesicular pH that controls the exocytotic machinery, probably regulating SNARE complex assembly during the synaptic vesicle priming step, and that, during the membrane fusion step, V0 might favor lipid mixing and fusion pore stability.
authors: Centre de Neurosciences Paris-Sud, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8195 and Université Paris-Sud, 91405, Orsay, France, nicolas.morel@u-psud.fr.
authors: Nicolas
authors: N
authors: Morel
authors: Sandrine
authors: S
authors: Poëa-Guyon
mesh_terms: D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D050600:SNARE Proteins / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D018377:Neurotransmitter Agents; D050600:SNARE Proteins; D025262:Vacuolar Proton-Translocating ATPases