+Search query
-Structure paper
Title | Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity. |
---|---|
Journal, issue, pages | Elife, Vol. 7, Year 2018 |
Publish date | Apr 13, 2018 |
Authors | Zohreh Farsi / Sindhuja Gowrisankaran / Matija Krunic / Burkhard Rammner / Andrew Woehler / Eileen M Lafer / Carsten Mim / Reinhard Jahn / Ira Milosevic / |
PubMed Abstract | Newly-formed synaptic vesicles (SVs) are rapidly acidified by vacuolar adenosine triphosphatases (vATPases), generating a proton electrochemical gradient that drives neurotransmitter loading. ...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. |
External links | Elife / PubMed:29652249 / PubMed Central |
Methods | EM (single particle) |
Resolution | 26.0 Å |
Structure data | EMDB-4335: |
Source |
|