Synaptotagmin I functions as a calcium sensor to synchronize neurotransmitter release

Neuron. 2002 Dec 5;36(5):897-908. doi: 10.1016/s0896-6273(02)01065-6.


To characterize Ca(2+)-mediated synaptic vesicle fusion, we analyzed Drosophila synaptotagmin I mutants deficient in specific interactions mediated by its two Ca(2+) binding C2 domains. In the absence of synaptotagmin I, synchronous release is abolished and a kinetically distinct delayed asynchronous release pathway is uncovered. Synapses containing only the C2A domain of synaptotagmin partially recover synchronous fusion, but have an abolished Ca(2+) cooperativity. Mutants that disrupt Ca(2+) sensing by the C2B domain have synchronous release with normal Ca(2+) cooperativity, but with reduced release probability. Our data suggest the Ca(2+) cooperativity of neurotransmitter release is likely mediated through synaptotagmin-SNARE interactions, while phospholipid binding and oligomerization trigger rapid fusion with increased release probability. These results indicate that synaptotagmin is the major Ca(2+) sensor for evoked release and functions to trigger synchronous fusion in response to Ca(2+), while suppressing asynchronous release.

MeSH terms

  • Animals
  • Binding Sites
  • Calcium / metabolism*
  • Calcium-Binding Proteins*
  • Drosophila melanogaster / physiology
  • Electric Stimulation
  • Embryo, Nonmammalian / physiology
  • Genotype
  • Membrane Fusion / physiology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / metabolism
  • Models, Biological
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurotransmitter Agents / metabolism*
  • Patch-Clamp Techniques
  • Protein Binding
  • Protein Structure, Tertiary
  • SNARE Proteins
  • Synapses / physiology
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism
  • Synaptotagmin I
  • Synaptotagmins
  • Time Factors
  • Vesicular Transport Proteins*


  • Calcium-Binding Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • SNARE Proteins
  • Synaptotagmin I
  • Vesicular Transport Proteins
  • Synaptotagmins
  • Calcium