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

Rab 家族小 G 蛋白在突触和上皮可塑性中的作用

• 批准号: 15390096
• 负责人: SASAKI Takuya
• 金额: $ 9.92万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390096/
• 关键词: synaptic plasticity; vesicular transport; Rab3A; Rab3 GAP; tight junction; claudin; occludin; Rab13; Rab; Claudin; occludin; JRAB; 低分子量G蛋白質; 小胞輸送; ノックアウトマウス; 高次神経機能; タイトジャクンション; 細胞間接着分子

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.

RAB家族G蛋白质由60多个家族细胞组成，在确定ULAR转运途径的规范中起着至关重要的作用。突触和突触前的质膜。在这项研究中，我们已经产生了Rab3间隙缺陷的小鼠，我们正在研究突触塑料中的Rab3间隙。调节TJ跨膜蛋白的囊泡转运。连续的内吞回到上皮细胞中的细胞表面。至关重要的调节剂，用于将闭合蛋白运输到TJ和上皮可塑性。

项目成果

Distinct roles of Rab3B and Rab13 in the polarized transport of apical, basolateral, and tight junctional membrane proteins to the plasma membrane

• DOI: 10.1016/s0006-291x(03)01358-5
• 发表时间: 2003-08-22
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Yamamoto, Y;Nishimura, N;Sasaki, T
• 通讯作者: Sasaki, T

Rab13 mediates the continuous endocytic recycling of occludin to the cell surface

• DOI: 10.1074/jbc.m406906200
• 发表时间: 2005-01-21
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Morimoto, S;Nishimura, N;Sasaki, T
• 通讯作者: Sasaki, T

Involvement of Cdc42 and Rac small G proteins in invadopodia formation of RPMI7951 cells

• DOI: 10.1111/j.1365-2443.2003.00695.x
• 发表时间: 2003-12-01
• 期刊: GENES TO CELLS
• 影响因子: 2.1
• 作者: Nakahara, H;Otani, T;Kogo, M
• 通讯作者: Kogo, M

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Mizuno, K.：“Rabring7，一种带有环指基序的新型 Rab7 靶蛋白”Mol.Biol.Cell。

Yamamoto, Y.: "Distinct roles of Rab3B and Rab13 in the polarized transport of apical, basolateral, and tight junctional membrane proteins to the plasma membrane"Biochem.Biophys.Res.Commun.. 308. 270-275 (2003)

Yamamoto, Y.：“Rab3B 和 Rab13 在顶端、基底外侧和紧密连接膜蛋白向质膜的极化运输中的不同作用”Biochem.Biophys.Res.Commun. 308. 270-275 (2003)