SNARE function analyzed in synaptobrevin/VAMP knockout mice

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