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Nature Research, Nature Structural and Molecular Biology, 10(19), p. 991-997, 2012

DOI: 10.1038/nsmb.2375

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Controlling synaptotagmin activity by electrostatic screening

Journal article published in 2012 by Yongsoo Park, Javier M. Hernandez, Geert van den Bogaart ORCID, Saheeb Ahmed, Matthew Holt ORCID, Dietmar Riedel, Reinhard Jahn
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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 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.