Role of the Rab family small G proteins in synaptic and epithelial plasticity

Rab家族小G蛋白在哺乳动物细胞中有60多个家族成员，在决定水疱转运途径的特异性方面起着至关重要的作用。Rab3A已被证明是一种调节Ca^<2+>依赖性突触囊泡胞外分泌的调节成分。Rab3A在gdp结合的无活性形式和gtp结合的活性形式之间循环，并在突触前神经末梢的细胞质与突触囊泡膜和突触前质膜之间易位。活化和易位受三个调节因子（Rab3 GDI、Rab3 GAP、Rab3 GEP）的调控。我们之前对Rab gdi α-缺陷和Rab3 gep缺陷小鼠的研究表明，这些调节因子参与调节短期突触可塑性。在这项研究中，我们成功地培育了Rab3 GAP缺陷小鼠，我们正在研究Rab3 GAP在突触可塑性中的作用。Rab13定位于极化上皮细胞的紧密连接（TJs），但其功能尚不清楚。在本研究中，我们研究了Rab13在调节TJ跨膜蛋白的囊泡运输中的作用。在胞外通路中，我们发现Rab13指导claudin-1的细胞表面转运，但不指导基底外侧跨膜蛋白、低密度脂蛋白受体的转运。我们还发现，在上皮细胞中，一池闭塞蛋白被持续内吞并循环回到细胞表面。结果表明Rab13特异性调节occludin的内吞循环。此外，我们发现Rab13不影响转铁蛋白受体的再循环，它被再循环到基侧质膜结构域。我们分离出一种与gtp结合形式的Rab13特异性相互作用的蛋白质，而不是与gdp结合形式相互作用的蛋白质。我们的研究结果表明，Rab13是一个重要的调节occludin和claudin转运到TJs和上皮可塑性。

The Rab family small G proteins, which consist of more than 60 family members in mammalian cells, play a crucial role in determining the specificity of vesicular transport pathways. Rab3A has been shown to be a modulatory component which regulates Ca^<2+>-dependent synaptic vesicle exocytosis. Rab3A cycles between the GDP-bound inactive form and the GTP-bound active form and translocates between the cytosol of the presynaptic nerve terminal and the membranes of synaptic vesicles and the presynaptic plasma membrane. The activation and the translocation are regulated by three regulators (Rab GDI, Rab3 GAP, Rab3 GEP). Our previous studies on Rab GDIα-deficient and Rab3 GEP-deficient mice revealed that these regulators are involved in modulating short-term synaptic plasticity. In this study, we have succeeded in generating Rab3 GAP-deficient mice and we are investigating the role of Rab3 GAP in synaptic plasticity. Rab13 localizes to tight junctions (TJs) in polarized epithelial cells, but its function is poorly understood. In the present study, we have examined the role of Rab13 in regulating the vesicular transport of TJ transmembrane proteins. In the exocytotic pathways, we found that Rab13 directs the cell-surface transport of claudin-1, but not a basolateral transmembrane protein, low-density lipoprotein receptor. We have also found that a pool of occludin was continuously endocytosed and recycled back to the cell-surface in epithelial cells. Our results indicated that Rab13 specifically regulated the endocytic recycling of occludin. Furthermore, we found that Rab13 did not affect the recycling of transferrin receptor, that was recycled to the basolateral plasma membrane domain. We isolated a protein that specifically interacted with the GTP-bound form of Rab13, but not its GDP-bound form. Our results suggest that Rab13 is a crucial regulator for the transport of occludin and claudins to TJs and for the epithelial plasticity.