SNARE function analyzed in synaptobrevin/VAMP knockout mice

SNARE function analyzed in synaptobrevin/VAMP knockout mice
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DOI:
10.1126/science.1064335
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发表时间:
2001-11-02
期刊:
影响因子:
56.9
通讯作者:
Kavalali, ET
Kavalali, ET
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Schoch, S;Deák, F;Kavalali, ET

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SNARES(可溶性NSF附着蛋白受体)被公认为膜融合反应的中心成分,但其确切功能仍是个谜。相互竞争的假说表明,圈套在调节融合的特异性、催化融合或实际执行融合中所起的作用。我们产生了缺乏Synaptobrevin/VAMP 2的基因敲除小鼠,Synaptobrevin/VAMP 2是负责前脑突触中突触小泡融合的囊泡陷阱蛋白,以利用电生理学的精细时间分辨率来测量融合。在没有突触素2的情况下,自发性突触囊泡融合和高渗蔗糖诱导的突触小泡融合减少约10倍,而钙离子触发的快速融合减少100倍以上。因此,Synaptobrevin 2可能在催化融合反应和稳定融合中间体方面发挥作用,但对突触融合并不是绝对必需的。
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 similar to 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.