Vesicular restriction of synaptobrevin suggests a role for calcium in membrane fusion

Kuang Hu, Joe Carroll, Sergei Fedorovich, Colin Rickman, Andrei Sukhodub, Bazbek Davletov

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Release of neurotransmitter occurs when synaptic vesicles fuse with the plasma membrane. This neuronal exocytosis is triggered by calcium and requires three SNARE (soluble-N-ethylmaleimide-sensitive factor attachment protein receptors) proteins: synaptobrevin (also known as VAMP) on the synaptic vesicle, and syntaxin and SNAP-25 on the plasma membrane. Neuronal SNARE proteins form a parallel four-helix bundle that is thought to drive the fusion of opposing membranes. As formation of this SNARE complex in solution does not require calcium, it is not clear what function calcium has in triggering SNARE-mediated membrane fusion. We now demonstrate that whereas syntaxin and SNAP-25 in target membranes are freely available for SNARE complex formation, availability of synaptobrevin on synaptic vesicles is very limited. Calcium at micromolar concentrations triggers SNARE complex formation and fusion between synaptic vesicles and reconstituted target membranes. Although calcium does promote interaction of SNARE proteins between opposing membranes, it does not act by releasing synaptobrevin from synaptic vesicle restriction. Rather, our data suggest a mechanism in which calcium-triggered membrane apposition enables syntaxin and SNAP-25 to engage synaptobrevin, leading to membrane fusion.
Original languageEnglish
Pages (from-to)646-650
Number of pages5
JournalNature
Volume415
Issue number6872
DOIs
Publication statusPublished - 7 Feb 2002

Keywords

  • Animals
  • Calcium
  • Exocytosis
  • Liposomes
  • Membrane Fusion
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Qa-SNARE Proteins
  • R-SNARE Proteins
  • Rats
  • SNARE Proteins
  • Synaptic Membranes
  • Synaptic Transmission
  • Synaptic Vesicles
  • Synaptosomal-Associated Protein 25
  • Vesicular Transport Proteins

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    Hu, K., Carroll, J., Fedorovich, S., Rickman, C., Sukhodub, A., & Davletov, B. (2002). Vesicular restriction of synaptobrevin suggests a role for calcium in membrane fusion. Nature, 415(6872), 646-650. https://doi.org/10.1038/415646a