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  • The EMBO Journal (2006) 25, 2039 - 2050
  • doi:10.1038/sj.emboj.7601103

Published online: 27 April 2006

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

Zhiping P Panga, Jianyuan Suna, Josep Rizo, Anton Maximov and Thomas C Südhof

  1. Departments of Molecular Genetics, Pharmacology, and Biochemistry, Center for Basic Neuroscience, Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX, USA

Correspondence to:

Thomas C Südhof, Department of Molecular Genetics, Center for Basic Neuroscience, Howard Hughes Medical Institute, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9111 USA. Tel.: +1 214 648 1876; Fax: +1 214 648 1879; E-mail: thomas.sudhof@utsouthwestern.edu

aThese authors contributed equally to this work

Received 9 January 2006; Accepted 28 March 2006

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.

  • Keywords:

    • Calyx of Held,
    • neuromuscular junctions,
    • synaptic transmission,
    • synaptotagmin