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Search: onr:"swepub:oai:DiVA.org:kth-227777" > Gowrisankaran Sindhuja > Clathrin coat contr...

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Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity

Farsi, Zohreh (author)
Max Planck Inst Biophys Chem, Dept Neurobiol, Gottingen, Germany.;Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Berlin, Germany.
Gowrisankaran, Sindhuja (author)
Univ Med Ctr Gottingen, European Neurosci Inst, Synapt Vesicle Dynam Grp, Gottingen, Germany.
Krunic, Matija (author)
Univ Med Ctr Gottingen, European Neurosci Inst, Synapt Vesicle Dynam Grp, Gottingen, Germany.
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Rammner, Burkhard (author)
Sciloop, Hamburg, Germany.
Woehler, Andrew (author)
Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Berlin, Germany.
Lafer, Eileen M. (author)
Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem & Struct Biol, San Antonio, TX 78229 USA.;Univ Texas Hlth Sci Ctr San Antonio, Ctr Biomed Neurosci, San Antonio, TX 78229 USA.
Mim, Carsten (author)
KTH,Medicinteknik och hälsosystem
Jahn, Reinhard (author)
Max Planck Inst Biophys Chem, Dept Neurobiol, Gottingen, Germany.
Milosevic, Ira (author)
Univ Med Ctr Gottingen, European Neurosci Inst, Synapt Vesicle Dynam Grp, Gottingen, Germany.
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Max Planck Inst Biophys Chem, Dept Neurobiol, Gottingen, Germany;Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Berlin, Germany. Univ Med Ctr Gottingen, European Neurosci Inst, Synapt Vesicle Dynam Grp, Gottingen, Germany. (creator_code:org_t)
ELIFE SCIENCES PUBLICATIONS LTD, 2018
2018
English.
In: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 7
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

NATURVETENSKAP  -- Biologi -- Biofysik (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biophysics (hsv//eng)

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