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Science 2 November 2001:
Vol. 294. no. 5544, pp. 1117 - 1122
DOI: 10.1126/science.1064335
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SNARE Function Analyzed in Synaptobrevin/VAMP Knockout Mice

Susanne Schoch,14* Ferenc Deák,14* Andreas Königstorfer,5* Marina Mozhayeva,1 Yildirim Sara,1 Thomas C. Südhof,124dagger Ege T. Kavalali13dagger

SNAREs (soluble NSF-attachment protein receptors) are generally acknowledged as central components of membrane fusion reactions, but their precise function has remained enigmatic. Competing hypotheses suggest roles for SNAREs in mediating the specificity of fusion, catalyzing fusion, or actually executing fusion. We generated knockout mice lacking synaptobrevin/VAMP 2, the vesicular SNARE protein responsible for synaptic vesicle fusion in forebrain synapses, to make use of the exquisite temporal resolution of electrophysiology in measuring fusion. In the absence of synaptobrevin 2, spontaneous synaptic vesicle fusion and fusion induced by hypertonic sucrose were decreased ~10-fold, but fast Ca2+-triggered fusion was decreased more than 100-fold. Thus, synaptobrevin 2 may function in catalyzing fusion reactions and stabilizing fusion intermediates but is not absolutely required for synaptic fusion.

1 Center for Basic Neuroscience, Departments of
2 Molecular Genetics and
3 Physiology, and
4 Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
5 Department of Molecular Neurobiology, Max-Planck-Institut für Experimentelle Medizin, 37075 Göttingen, Germany.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: Thomas.Sudhof{at}UTSouthwestern.edu, Ege.Kavalali{at}UTSouthwestern.edu

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