Stahl B, Chou J H, Li C, Südhof T C, Jahn R
Department of Pharmacology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
EMBO J. 1996 Apr 15;15(8):1799-809.
GTP activates the interaction between the synaptic vesicle proteins rabphilin and rab3. This raises the question of whether rabphilin is a resident vesicle protein that recruits rab3 in a stage-dependent fashion, or if it is instead an effector protein recruited by rab3. We now show that rabphilin, like rab3, dissociates from synaptic vesicles after exocytosis in a manner requiring both Ca2+ and membrane fusion. Rabphilin interacts with GTP-rab3 via a N-terminal domain comprising a novel Zn2+(-)finger motif, and this interaction is essential for rabphilin binding to synaptic vesicles. Thus, in the same way that ras recruits raf to the plasma membrane, rab3 reversibly recruits rabphilin to synaptic vesicles in a stage-dependent manner. These results reveal an unexpected similarity between the molecular mechanisms by which small G protein function in recruiting effector proteins to membranes during membrane traffic and signal transduction.
鸟苷三磷酸（GTP）激活突触小泡蛋白rabphilin和rab3之间的相互作用。这就提出了一个问题，即rabphilin是一种以阶段依赖方式招募rab3的驻留小泡蛋白，还是相反，它是由rab3招募的效应蛋白。我们现在表明，rabphilin与rab3一样，在胞吐作用后以需要Ca2+和膜融合的方式从突触小泡中解离。Rabphilin通过包含新型锌2+（-）指基序的N端结构域与GTP-rab3相互作用，这种相互作用对于rabphilin与突触小泡的结合至关重要。因此，就像ras将raf招募到质膜一样，rab3以阶段依赖的方式将rabphilin可逆地招募到突触小泡。这些结果揭示了小G蛋白在膜运输和信号转导过程中招募效应蛋白到膜上的分子机制之间意想不到的相似性。
