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-Structure paper
タイトル | Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity. |
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ジャーナル・号・ページ | Elife, Vol. 7, Year 2018 |
掲載日 | 2018年4月13日 |
著者 | Zohreh Farsi / Sindhuja Gowrisankaran / Matija Krunic / Burkhard Rammner / Andrew Woehler / Eileen M Lafer / Carsten Mim / Reinhard Jahn / Ira Milosevic / |
PubMed 要旨 | 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. |
リンク | Elife / PubMed:29652249 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 26.0 Å |
構造データ | EMDB-4335: |
由来 |
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