Science · 2001 · 655 citations · 35 references
SNAREs are key membrane fusion proteins, yet their exact role—whether mediating specificity, catalyzing, or executing fusion—remains debated. The study aimed to dissect synaptobrevin/VAMP2 function by creating knockout mice lacking this vesicular SNARE. Electrophysiological recordings in these mice provided high‑resolution measurements of spontaneous, sucrose‑induced, and Ca²⁺‑triggered vesicle fusion events. Loss of synaptobrevin 2 reduced spontaneous and sucrose‑induced fusion by ~10‑fold and Ca²⁺‑triggered fusion by >100‑fold, indicating it catalyzes fusion and stabilizes intermediates but is not essential for synaptic release.
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 Ca 2+ -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.
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SNAREpins: Minimal Machinery for Membrane Fusion
Thomas Weber, Boris V. Zemelman, James A. McNew et al. · Cell · 1998 · 2.5K citations · Full text
Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse
Martin Geppert, Yukiko Goda, Robert E. Hammer et al. · Cell · 1994 · 1.5K citations