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  Controlling synaptotagmin activity by electrostatic screening.

Park, Y., Hernandez, J. M., van den Bogaart, G., Ahmed, S., Holt, M., Riedel, D., et al. (2012). Controlling synaptotagmin activity by electrostatic screening. Nature Structural and Molecular Biology, 19(10), 991-997. doi:10.1038/nsmb.2375.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000F-EBFE-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-1DED-6
Genre: Journal Article

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 Creators:
Park, Y., Author
Hernandez, J. M.1, Author              
van den Bogaart, G.1, Author              
Ahmed, S.1, Author              
Holt, M.1, Author              
Riedel, D.2, Author              
Jahn, R.1, Author              
Affiliations:
1Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society, ou_578595              
2Facility for Electron Microscopy, MPI for biophysical chemistry, Max Planck Society, ou_578615              

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 Abstract: Exocytosis of neurosecretory vesicles is mediated by the SNARE (soluble N-ethylmaleimide–sensitive factor attachment protein receptor) proteins syntaxin-1, synaptobrevin and SNAP-25, with synaptotagmin functioning as the major Ca2+ sensor for triggering membrane fusion. Here we show that bovine chromaffin granules readily fuse with large unilamellar liposomes in a SNARE-dependent manner. Fusion is enhanced by Ca2+, but only when the target liposomes contain phosphatidylinositol-4,5-bisphosphate and when polyphosphate anions, such as nucleotides or pyrophosphate, are present. Ca2+-dependent enhancement is mediated by endogenous synaptotagmin-1. Polyphosphates operate by an electrostatic mechanism that reverses an inactivating cis association of synaptotagmin-1 with its own membrane without affecting trans binding. Hence, the balancing of trans- and cis-membrane interactions of synaptotagmin-1 could be a crucial element in the pathway of Ca2+-dependent exocytosis.

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Language(s): eng - English
 Dates: 2012-09-022012
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1038/nsmb.2375
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Title: Nature Structural and Molecular Biology
Source Genre: Journal
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Pages: - Volume / Issue: 19 (10) Sequence Number: - Start / End Page: 991 - 997 Identifier: -