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TitleClathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity.
Journal, issue, pagesElife, Vol. 7, Year 2018
Publish dateApr 13, 2018
AuthorsZohreh Farsi / Sindhuja Gowrisankaran / Matija Krunic / Burkhard Rammner / Andrew Woehler / Eileen M Lafer / Carsten Mim / Reinhard Jahn / Ira Milosevic /
PubMed AbstractNewly-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 linksElife / PubMed:29652249 / PubMed Central
MethodsEM (single particle)
Resolution26.0 Å
Structure data

EMDB-4335:
Clathrin Coated Vesicle of 850 angstrom from mouse brain
Method: EM (single particle) / Resolution: 26.0 Å

Source
  • Mus musculoides (Temminck's mouse)

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