Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity
Item Type: | Article |
---|
Title: | Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity |
---|
Creators Name: | Farsi, Z. and Gowrisankaran, S. and Krunic, M. and Rammner, B. and Woehler, A. and Lafer, E.M. and Mim, C. and 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 |
---|
Source: | eLife |
---|
ISSN: | 2050-084X |
---|
Publisher: | eLife Sciences Publications |
---|
Volume: | 7 |
---|
Page Range: | e32569 |
---|
Date: | 13 April 2018 |
---|
Official Publication: | https://doi.org/10.7554/eLife.32569 |
---|
PubMed: | View item in PubMed |
---|
Repository Staff Only: item control page
Downloads per month over past year
|