Controlling synaptotagmin activity by electrostatic screening

Y. Park, J.M. Hernandez, Geert van den Bogaart, S. Ahmed, D. Riedel, Reinhard Jahn

Research output: Contribution to journalArticleAcademicpeer-review

53 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)991-997
Number of pages7
JournalNature Structural & Molecular Biology
Volume19
Issue number10
DOIs
Publication statusPublished - 19-Oct-2012
Externally publishedYes

Keywords

  • synaptotagmin
  • electrostatic screening
  • exocytosis
  • SNAREs

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