Are neuronal SNARE proteins Ca2+ sensors?

Xiaocheng Chen, Jiong Tang, Thomas C. Sudhof, Josep Rizo

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The neuronal SNARE complex formed by synaptobrevin, syntaxin and SNAP-25 plays a central role in Ca2+-triggered neurotransmitter release. The SNARE complex contains several potential Ca2+-binding sites on the surface, suggesting that the SNAREs may be involved directly in Ca 2+-binding during release. Indeed, overexpression of SNAP-25 bearing mutations in two putative Ca2+ ligands (E170A/Q177A) causes a decrease in the Ca2+-cooperativity of exocytosis in chromaffin cells. To test whether the SNARE complex might function in Ca2+-sensing, we analyzed its Ca2+-binding properties using transverse relaxation optimized spectroscopy (TROSY)-based NMR methods. Several Ca2+- binding sites are found on the surface of the SNARE complex, but most of them are not specific for Ca2+ and all have very low affinity. Moreover, we find that the E170A/Q177A SNAP-25 mutation does not alter interactions between the SNAREs and the Ca2+ sensor synaptotagmin 1, but severely impairs SNARE complex assembly. These results suggest that the SNAREs do not act directly as Ca2+ receptors but SNARE complex assembly is coupled tightly to Ca2+-sensing during neurotransmitter release.

Original languageEnglish (US)
Pages (from-to)145-158
Number of pages14
JournalJournal of Molecular Biology
Volume347
Issue number1
DOIs
Publication statusPublished - Mar 18 2005

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Keywords

  • Ca-binding
  • Neurotransmitter release
  • Protein NMR
  • SNAREs
  • TROSY

ASJC Scopus subject areas

  • Virology

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