{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Park Y"],"funding":["NIGMS NIH HHS"],"pagination":["991-7"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3465474"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(10)"],"pubmed_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 Ca(2+) 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 Ca(2+), but only when the target liposomes contain phosphatidylinositol-4,5-bisphosphate and when polyphosphate anions, such as nucleotides or pyrophosphate, are present. Ca(2+)-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 Ca(2+)-dependent exocytosis."],"journal":["Nature structural & molecular biology"],"pubmed_title":["Controlling synaptotagmin activity by electrostatic screening."],"pmcid":["PMC3465474"],"funding_grant_id":["P01 GM072694","2 P01 GM072694-06A1"],"pubmed_authors":["Jahn R","Park Y","Ahmed S","van den Bogaart G","Holt M","Hernandez JM","Riedel D"],"additional_accession":[]},"is_claimable":false,"name":"Controlling synaptotagmin activity by electrostatic screening.","description":"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 Ca(2+) 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 Ca(2+), but only when the target liposomes contain phosphatidylinositol-4,5-bisphosphate and when polyphosphate anions, such as nucleotides or pyrophosphate, are present. Ca(2+)-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 Ca(2+)-dependent exocytosis.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Oct","modification":"2025-04-05T12:55:05.427Z","creation":"2019-03-27T00:58:49Z"},"accession":"S-EPMC3465474","cross_references":{"pubmed":["22940675"],"doi":["10.1038/nsmb.2375"]}}