1. Controlling synaptotagmin activity by electrostatic screening.
- Author
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Park Y, Hernandez JM, van den Bogaart G, Ahmed S, Holt M, Riedel D, and Jahn R
- Subjects
- Adenosine Triphosphate metabolism, Animals, Calcium metabolism, Cattle, Chromaffin Granules chemistry, Chromaffin Granules drug effects, Exocytosis physiology, Liposomes chemistry, Liposomes metabolism, Membrane Fusion, Phosphatidylinositol 4,5-Diphosphate metabolism, Phospholipids chemistry, Phospholipids metabolism, Polyphosphates chemistry, Polyphosphates metabolism, Rats, SNARE Proteins metabolism, Static Electricity, Synaptosomal-Associated Protein 25 metabolism, Syntaxin 1 metabolism, Chromaffin Granules metabolism, Synaptotagmin I metabolism
- 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.
- Published
- 2012
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