SNARE proteins: one to fuse and three to keep the nascent fusion pore open

Science. 2012 Mar 16;335(6074):1355-9. doi: 10.1126/science.1214984.

Abstract

Neurotransmitters are released through nascent fusion pores, which ordinarily dilate after bilayer fusion, preventing consistent biochemical studies. We used lipid bilayer nanodiscs as fusion partners; their rigid protein framework prevents dilation and reveals properties of the fusion pore induced by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor). We found that although only one SNARE per nanodisc is required for maximum rates of bilayer fusion, efficient release of content on the physiologically relevant time scale of synaptic transmission apparently requires three or more SNARE complexes (SNAREpins) and the native transmembrane domain of vesicle-associated membrane protein 2 (VAMP2). We suggest that several SNAREpins simultaneously zippering their SNARE transmembrane helices within the freshly fused bilayers provide a radial force that prevents the nascent pore from resealing during synchronous neurotransmitter release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Diffusion
  • Lipid Bilayers*
  • Liposomes
  • Membrane Fusion*
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Mice
  • Neurotransmitter Agents / metabolism
  • Protein Structure, Tertiary
  • Proteolipids / chemistry
  • Rats
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • SNARE Proteins / chemistry*
  • SNARE Proteins / metabolism*
  • Synaptic Transmission
  • Synaptic Vesicles / chemistry*
  • Synaptic Vesicles / metabolism
  • Synaptosomal-Associated Protein 25 / chemistry
  • Synaptosomal-Associated Protein 25 / metabolism
  • Syntaxin 1 / chemistry
  • Syntaxin 1 / metabolism
  • Vesicle-Associated Membrane Protein 2 / chemistry*
  • Vesicle-Associated Membrane Protein 2 / metabolism*

Substances

  • Lipid Bilayers
  • Liposomes
  • Membrane Proteins
  • Neurotransmitter Agents
  • Proteolipids
  • Recombinant Fusion Proteins
  • SNARE Proteins
  • Snap25 protein, mouse
  • Synaptosomal-Associated Protein 25
  • Syntaxin 1
  • Vesicle-Associated Membrane Protein 2
  • proteoliposomes
  • Calcium