Neurotransmitter release: the dark side of the vacuolar-H+ATPase.
Vacuolar-H+ATPase (V-ATPase) is a complex enzyme with numerous subunits organized in two domains. The membrane domain V0 contains a proteolipid hexameric ring that translocates protons when ATP is hydrolysed by the catalytic cytoplasmic sector (V1). In nerve terminals, V-ATPase generates an electrochemical proton gradient that is acid and positive inside synaptic vesicles. It is used by specific neurotransmitter-proton antiporters to accumulate neurotransmitters inside their storage organelles. During synaptic activity, neurotransmitters are released from synaptic vesicles docked at specialized portions of the presynaptic plasma membrane, the active zones. A fusion pore opens that allows the neurotransmitter to be released from the synaptic vesicle lumen into the synaptic cleft. We briefly review experimental data suggesting that the membrane domain of V-ATPase could be such a fusion pore. We also discuss the functional implications for quantal neurotransmitter release of the sequential use of the same V-ATPase membrane domain in two different events, neurotransmitter accumulation in synaptic vesicles first, and then release from these organelles during synaptic activity.
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, 91198 Gif sur Yvette, France. nicolas.morel@nbcm.cnrs-gif.fr
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D000818:Animals; D008561:Membrane Fusion; D018377:Neurotransmitter Agents / Q000096:biosynthesis / Q000378:metabolism*; D013570:Synaptic Membranes / Q000737:chemistry; D013572:Synaptic Vesicles / Q000737:chemistry / Q000201:enzymology; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000502:physiology*
D018377:Neurotransmitter Agents; D025262:Vacuolar Proton-Translocating ATPases