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Journal Article

Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity.

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Farsi,  Z.
Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Jahn,  R.
Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Citation

Farsi, Z., Gowrisankaran, S., Krunic, M., Rammner, B., Woehler, A., Lafer, E. M., et al. (2018). Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity. eLife, 7: e32569. doi:10.7554/eLife.32569.


Cite as: http://hdl.handle.net/21.11116/0000-0001-270F-4
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.