A possible docking and fusion particle for synaptic transmission

Nature. 1995 Dec 14;378(6558):733-6. doi: 10.1038/378733a0.


Several proteins have been implicated in the rapid (millisecond) calcium-controlled release of transmitters at nerve endings, including soluble N-ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment protein (alpha-SNAP), the synaptic SNAP receptor (SNARE) and the calcium-binding protein synaptotagmin, which may function as a calcium sensor in exocytosis. A second SNAP isoform (beta-SNAP), which is 83% identical to alpha-SNAP, is highly expressed in brain, but its role is still unclear. Here we show that these proteins assemble cooperatively to form a docking and fusion complex. beta-SNAP (but not alpha-SNAP) binds synaptotagmin and recruits NSF, indicating that the complex may link the process of membrane fusion to calcium entry by attaching a specialized fusion protein (beta-SNAP) to a calcium sensor (synaptotagmin). Polyphosphoinositols that block transmitter release, inositol 1,3,4,5-tetrakisphosphate (InsP4), inositol 1,3,4,5,6-pentakisphosphate (InsP5) and inositol 1,2,3,4,5,6-hexakisphosphate (InsP6), also block the assembly of the particle by preventing beta-SNAP from binding to synaptotagmin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium / metabolism
  • Calcium-Binding Proteins*
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Glutathione Transferase / metabolism
  • Inositol Phosphates / metabolism
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / physiology*
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • N-Ethylmaleimide-Sensitive Proteins
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Protein Binding
  • Recombinant Fusion Proteins / metabolism
  • SNARE Proteins
  • Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
  • Synaptic Transmission / physiology*
  • Synaptotagmins
  • Vesicular Transport Proteins*


  • Calcium-Binding Proteins
  • Carrier Proteins
  • Inositol Phosphates
  • Membrane Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins
  • SNARE Proteins
  • Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
  • Vesicular Transport Proteins
  • Synaptotagmins
  • Glutathione Transferase
  • N-Ethylmaleimide-Sensitive Proteins
  • Calcium