Kinetics of synaptotagmin responses to Ca2+ and assembly with the core SNARE complex onto membranes

Neuron. 1999 Oct;24(2):363-76. doi: 10.1016/s0896-6273(00)80850-8.


The synaptic vesicle protein synaptotagmin I binds Ca2+ and is required for efficient neurotransmitter release. Here, we measure the response time of the C2 domains of synaptotagmin to determine whether synaptotagmin is fast enough to function as a Ca2+ sensor for rapid exocytosis. We report that synaptotagmin is "tuned" to sense Ca2+ concentrations that trigger neuronal exocytosis. The speed of response is unique to synaptotagmin I and readily satisfies the kinetic constraints of synaptic vesicle membrane fusion. We further demonstrate that Ca2+ triggers penetration of synaptotagmin into membranes and simultaneously drives assembly of synaptotagmin onto the base of the ternary SNARE (soluble N-ethylmaleimide-sensitive fusion protein [NSF] attachment receptor) complex, near the transmembrane anchor of syntaxin. These data support a molecular model in which synaptotagmin triggers exocytosis through its interactions with membranes and the SNARE complex.

Publication types

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

MeSH terms

  • Animals
  • Calcium / physiology*
  • Calcium-Binding Proteins*
  • Kinetics
  • Membrane Fusion / physiology
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / metabolism*
  • Membranes / metabolism
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Rats
  • Repetitive Sequences, Nucleic Acid
  • SNARE Proteins
  • Sequence Homology
  • Synaptic Vesicles / metabolism*
  • Synaptotagmin I
  • Synaptotagmins
  • Vesicular Transport Proteins*


  • Calcium-Binding Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • SNARE Proteins
  • Synaptotagmin I
  • Syt1 protein, rat
  • Vesicular Transport Proteins
  • Synaptotagmins
  • Calcium