Synaptotagmin-1, -2, and -9: Ca(2+) sensors for fast release that specify distinct presynaptic properties in subsets of neurons

Neuron. 2007 May 24;54(4):567-81. doi: 10.1016/j.neuron.2007.05.004.


Synaptotagmin-1 and -2 are known Ca(2+) sensors for fast synchronous neurotransmitter release, but the potential Ca(2+)-sensor functions of other synaptotagmins in release remain uncharacterized. We now show that besides synaptotagmin-1 and -2, only synaptotagmin-9 (also called synaptotagmin-5) mediates fast Ca(2+) triggering of release. Release induced by the three different synaptotagmin Ca(2+) sensors exhibits distinct kinetics and apparent Ca(2+) sensitivities, suggesting that the synaptotagmin isoform expressed by a neuron determines the release properties of its synapses. Conditional knockout mice producing GFP-tagged synaptotagmin-9 revealed that synaptotagmin-9 is primarily expressed in the limbic system and striatum. Acute deletion of synaptotagmin-9 in striatal neurons severely impaired fast synchronous release without changing the size of the readily-releasable vesicle pool. These data show that in mammalian brain, only synaptotagmin-1, -2, and -9 function as Ca(2+) sensors for fast release, and that these synaptotagmins are differentially expressed to confer distinct release properties onto synapses formed by defined subsets of neurons.

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium / metabolism*
  • Cells, Cultured
  • Corpus Striatum / cytology
  • Gene Expression Regulation / genetics
  • Green Fluorescent Proteins / metabolism
  • Inhibitory Postsynaptic Potentials / genetics
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Neurons / classification*
  • Neurons / cytology*
  • Patch-Clamp Techniques / methods
  • Presynaptic Terminals / metabolism*
  • Synapsins / metabolism
  • Synaptotagmin I / metabolism
  • Synaptotagmin II / metabolism
  • Synaptotagmins / genetics
  • Synaptotagmins / metabolism*


  • Microtubule-Associated Proteins
  • Mtap2 protein, mouse
  • Synapsins
  • Synaptotagmin I
  • Synaptotagmin II
  • Synaptotagmins
  • Green Fluorescent Proteins
  • Calcium