Li C, Takei K, Geppert M, Daniell L, Stenius K, Chapman E R, Jahn R, De Camilli P, Südhof T C
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Neuron. 1994 Oct;13(4):885-98. doi: 10.1016/0896-6273(94)90254-2.
rab3A, a low molecular weight GTP-binding protein of synaptic vesicles with a putative function in synaptic vesicle docking, interacts in a GTP-dependent manner with rabphilin-3A, a peripheral membrane protein that binds Ca2+ and phospholipids. We now show that rabphilin-3A is an evolutionarily conserved synaptic vesicle protein that is attached to synaptic vesicle membranes via its N terminus and exhibits a heterogeneous distribution among synapses. In rab3A-deficient mice, rabphilin-3A is decreased in synapses belonging to neurons that primarily express rab3A and accumulates in the perikarya of these neurons. In contrast, neurons expressing significant levels of rab3C still contain normal levels of rabphilin-3A in a synaptic pattern, and rabphilin-3A binds rab3C in vitro. These results suggest that analogous to the membrane recruitment of raf by ras, rab3A and rab3C may function in recruiting rabphilin-3A to the synaptic vesicle membrane in a GTP-dependent manner.
Rab3A是一种低分子量的突触小泡GTP结合蛋白，在突触小泡对接中可能发挥作用，它以GTP依赖的方式与rabphilin-3A相互作用，rabphilin-3A是一种结合Ca2+和磷脂的外周膜蛋白。我们现在表明，rabphilin-3A是一种进化上保守的突触小泡蛋白，通过其N末端附着于突触小泡膜，并在突触间呈现异质性分布。在rab3A缺陷小鼠中，rabphilin-3A在主要表达rab3A的神经元所属的突触中减少，并在这些神经元的胞体中积累。相反，表达大量rab3C的神经元在突触模式中仍含有正常水平的rabphilin-3A，并且rabphilin-3A在体外与rab3C结合。这些结果表明，类似于ras对raf的膜募集，rab3A和rab3C可能以GTP依赖的方式在将rabphilin-3A募集到突触小泡膜中发挥作用。
