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Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity

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Item Type:Article
Title:Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity
Creators Name:Farsi, Z., Gowrisankaran, S., Krunic, M., Rammner, B., Woehler, A., Lafer, E.M., Mim, C., Jahn, R. and Milosevic, I.
Abstract:Newly-formed synaptic vesicles (SVs) are rapidly acidified by vacuolar adenosine triphosphatases (vATPases), generating a proton electrochemical gradient that drives neurotransmitter loading. Clathrin-mediated endocytosis is needed for the formation of new SVs, yet it is unclear when endocytosed vesicles acidify and refill at the synapse. Here, we isolated clathrin-coated vesicles (CCVs) from mouse brain to measure their acidification directly at the single vesicle level. We observed that the ATP-induced acidification of CCVs was strikingly reduced in comparison to SVs. Remarkably, when the coat was removed from CCVs, uncoated vesicles regained ATP-dependent acidification, demonstrating that CCVs contain the functional vATPase, yet its function is inhibited by the clathrin coat. Considering the known structures of the vATPase and clathrin coat, we propose a model in which the formation of the coat surrounds the vATPase and blocks its activity. Such inhibition is likely fundamental for the proper timing of SV refilling.
Keywords:Adenosine Triphosphate, Brain, Clathrin, Clathrin-Coated Vesicles, Hydrolysis, Synaptic Vesicles, Vacuolar Proton-Translocating ATPases, Animals, Mice
Publisher:eLife Sciences Publications
Page Range:e32569
Date:13 April 2018
Official Publication:https://doi.org/10.7554/eLife.32569
PubMed:View item in PubMed

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