Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered neurotransmitter release

EMBO J. 2006 May 17;25(10):2039-50. doi: 10.1038/sj.emboj.7601103. Epub 2006 Apr 27.


Synaptotagmin 2 resembles synaptotagmin 1, the Ca2+ sensor for fast neurotransmitter release in forebrain synapses, but little is known about synaptotagmin 2 function. Here, we describe a severely ataxic mouse strain that harbors a single, destabilizing amino-acid substitution (I377N) in synaptotagmin 2. In Calyx of Held synapses, this mutation causes a delay and a decrease in Ca2+-induced but not in hypertonic sucrose-induced release, suggesting that synaptotagmin 2 mediates Ca2+ triggering of evoked release in brainstem synapses. Unexpectedly, we additionally observed in synaptotagmin 2 mutant synapses a dramatic increase in spontaneous release. Synaptotagmin 1-deficient excitatory and inhibitory cortical synapses also displayed a large increase in spontaneous release, demonstrating that this effect was shared among synaptotagmins 1 and 2. Our data suggest that synaptotagmin 1 and 2 perform equivalent functions in the Ca2+ triggering of action potential-induced release and in the restriction of spontaneous release, consistent with a general role of synaptotagmins in controlling 'release slots' for synaptic vesicles at the active zone.

MeSH terms

  • Action Potentials / physiology
  • Amino Acid Sequence
  • Animals
  • Ataxia / genetics
  • Ataxia / metabolism
  • Brain / anatomy & histology
  • Calcium / metabolism*
  • In Vitro Techniques
  • Mice
  • Molecular Sequence Data
  • Neurons / cytology
  • Neurons / metabolism
  • Neurotransmitter Agents / metabolism*
  • Patch-Clamp Techniques
  • Point Mutation
  • Protein Denaturation
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Synapses / metabolism
  • Synaptic Transmission / physiology*
  • Synaptotagmin I / genetics
  • Synaptotagmin I / metabolism
  • Synaptotagmin II* / genetics
  • Synaptotagmin II* / metabolism


  • Neurotransmitter Agents
  • Synaptotagmin I
  • Synaptotagmin II
  • Syt1 protein, mouse
  • Syt2 protein, mouse
  • Calcium