SNARE function analyzed in synaptobrevin/VAMP knockout mice.
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 approximately 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.
Schoch
S
S
Center for Basic Neuroscience, Department of Molecular Genetics, Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Deák
F
F
Königstorfer
A
A
Mozhayeva
M
M
Sara
Y
Y
Südhof
T C
TC
Kavalali
E T
ET
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D006982:Hypertonic Solutions; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000502:physiology; D016548:Prosencephalon / Q000502:physiology; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D013395:Sucrose / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000502:physiology*; D033921:Vesicular Transport Proteins
D006982:Hypertonic Solutions; D008565:Membrane Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D013395:Sucrose; D011188:Potassium; D002118:Calcium