Mechanism of calcium-independent synaptotagmin binding to target SNAREs

Colin Rickman, Bazbek Davletov

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Synaptic vesicle exocytosis requires three SNARE (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor) proteins: syntaxin and SNAP-25 on the plasma membrane (t-SNAREs) and synaptobrevin/VAMP on the synaptic vesicles (v-SNARE). Vesicular synaptotagmin 1 is essential for fast synchronous SNARE-mediated exocytosis and interacts with the SNAREs in brain material. To uncover the step at which synaptotagmin becomes linked to the three SNAREs, we purified all four proteins from brain membranes and analyzed their interactions. Our study reveals that, in the absence of calcium, native synaptotagmin 1 binds the t-SNARE heterodimer, formed from syntaxin and SNAP-25. This interaction is both stoichiometric and of high affinity. Synaptotagmin contains two divergent but conserved C2 domains that can act independently in calcium-triggered phospholipid binding. We now show that both C2 domains are strictly required for the calcium-independent interaction with the t-SNARE heterodimer, indicating that the double C2 domain structure of synaptotagmin may have evolved to acquire a function beyond calcium/phospholipid binding.
Original languageEnglish
Pages (from-to)5501-5504
Number of pages4
JournalJournal of Biological Chemistry
Volume278
Issue number8
DOIs
Publication statusPublished - 21 Feb 2003

Keywords

  • Animals
  • Binding Sites
  • Calcium
  • Calcium-Binding Proteins
  • Cattle
  • Cerebral Cortex
  • Cytoplasm
  • Exocytosis
  • Membrane Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Protein Binding
  • SNARE Proteins
  • Substrate Specificity
  • Synaptic Vesicles
  • Synaptotagmin I
  • Synaptotagmins
  • Vesicular Transport Proteins

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