| First Author | Farsi Z | Year | 2018 |
| Journal | Elife | Volume | 7 |
| PubMed ID | 29652249 | Mgi Jnum | J:326654 |
| Mgi Id | MGI:7316540 | Doi | 10.7554/eLife.32569 |
| Citation | Farsi Z, et al. (2018) Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity. Elife 7:e32569 |
| abstractText | 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. |
