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.
Morel
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Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, 91198 Gif sur Yvette, France. nicolas.morel@nbcm.cnrs-gif.fr
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