title: Controlling synaptotagmin activity by electrostatic screening.
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.
authors.affiliation: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Yongsoo
authors.initials: Y
authors.lastname: Park
authors.forename: Javier M
authors.initials: JM
authors.lastname: Hernandez
authors.forename: Geert
authors.initials: G
authors.lastname: van den Bogaart
authors.forename: Saheeb
authors.initials: S
authors.lastname: Ahmed
authors.forename: Matthew
authors.initials: M
authors.lastname: Holt
authors.forename: Dietmar
authors.initials: D
authors.lastname: Riedel
authors.forename: Reinhard
authors.initials: R
authors.lastname: Jahn
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002837:Chromaffin Granules / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008561:Membrane Fusion; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D011122:Polyphosphates / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism; D055672:Static Electricity; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D050863:Synaptotagmin I / Q000378:metabolism*; D050827:Syntaxin 1 / Q000378:metabolism
chemical_list: D008081:Liposomes; D019269:Phosphatidylinositol 4,5-Diphosphate; D010743:Phospholipids; D011122:Polyphosphates; D050600:SNARE Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D050863:Synaptotagmin I; D050827:Syntaxin 1; D000255:Adenosine Triphosphate; D002118:Calcium