AI Article Synopsis

  • Newly-formed synaptic vesicles (SVs) rely on vATPases for rapid acidification, creating a proton gradient critical for loading neurotransmitters.
  • Clathrin-coated vesicles (CCVs) were isolated from mouse brain to investigate when these vesicles acidify and refill during synaptic activity.
  • The study found that while CCVs have functional vATPases, their acidification is inhibited by the clathrin coat, suggesting this inhibition is key for the timing of SV refilling.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935483PMC
http://dx.doi.org/10.7554/eLife.32569DOI Listing

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