Abstract
The vacuolar proton pump (V-ATPase) is a huge multi-subunit complex composed of two distinct non-covalently associated sectors. The cytosolic V1 sector hydrolyses ATP, providing the energy for the V0 membrane sector to translocate protons into the vesicle lumen. The proton gradient is then used by vesicular transporters to load synaptic vesicles with specific neurotransmitters. The primary role of the V-ATPase in vesicle loading is widely accepted. However, multiple studies in a variety of model organisms point to an additional general role of the V0 sector in downstream events, notably in regulating SNARE-mediated membrane fusion. This chapter outlines the molecular pharmacology of the V-ATPase and its role in the synaptic vesicle cycle. It then focuses specifically on molecular interactions between V0 subunits and synaptic vesicle trafficking proteins and reviews their relevance to late steps in neurotransmitter release. While this secondary role for the V-ATPase membrane sector is not yet fully established, we speculate that it could provide a regulatory link between vesicle filling and fusion, acting as a filter that allows loaded vesicles to engage the fusion machinery.
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El Far, O., Seagar, M. (2015). The Synaptic Vesicle V-ATPase: A Regulatory Link Between Loading and Fusion?. In: Mochida, S. (eds) Presynaptic Terminals. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55166-9_7
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