Regulatory mechanism of Rab14 and its effector proteins in post-Golgi membrane trafficking

Rab14及其效应蛋白在高尔基体后膜运输中的调控机制

• 批准号: 21770203
• 负责人: SHIN Hye-Won
• 金额: $ 2.91万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21770203/
• 关键词: 細胞; メンブレントラフィック; 小胞輸送; 低分子量GTPase; エンドソーム; 低分量GTPase; Small GTPase

Here, we report that Rab14 binds in a GTP-dependent manner to RUFY1/Rabip4, which had been originally identified as a Rab4 effector. Rab14 colocalizes well with Rab4 on peripheral endosomes. Depletion of Rab14, but not Rab4, causes dissociation of RUFY1 from endosomal membranes. Coexpression of RUFY1 with either Rab14 or Rab4 induces clustering and enlargement of endosomes, while a RUFY1 mutant lacking the Rab4-binding region does not induce a significant morphological change in the endosomal structures even when coexpressed with Rab14 or Rab4. These findings suggest that Rab14 and Rab4 act sequentially, together with RUFY1 ; Rab14 is required for recruitment of RUFY1 onto endosomal membranes, and subsequent RUFY1 interaction with Rab4 may allow endosomal tethering and fusion. Depletion of Rab14 or RUFY1, as well as Rab4, inhibits efficient recycling of endocytosed transferrin, suggesting that Rab14 and Rab4 regulate endosomal functions through cooperative interactions with their dual effector, RUFY1.

在这里，我们报告Rab 14以GTP依赖性方式结合RUFY 1/Rabip 4，RUFY 1/Rabip 4最初被鉴定为Rab 4效应子。Rab 14与Rab 4在外周核内体上共定位良好。Rab 14的缺失，而不是Rab 4，导致RUFY 1从内体膜上解离。RUFY 1与Rab 14或Rab 4的共表达诱导内体的聚集和扩大，而缺乏Rab 4结合区域的RUFY 1突变体即使与Rab 14或Rab 4共表达也不会诱导内体结构的显著形态学变化。这些发现表明Rab 14和Rab 4与RUFY 1一起顺序作用; Rab 14是将RUFY 1募集到内体膜上所必需的，随后RUFY 1与Rab 4的相互作用可能允许内体束缚和融合。Rab 14或RUFY 1以及Rab 4的耗竭抑制内吞转铁蛋白的有效再循环，表明Rab 14和Rab 4通过与其双重效应子RUFY 1的协同相互作用来调节内体功能。

项目成果

Small GTPase ARF3 is involved in lysosomal degradation pathway

小GTP酶ARF3参与溶酶体降解途径

• 发表时间: 2009
• 作者: Oinuma;I.;Ito;Y.;Katoh;H.;Negishi;M.;申惠媛
• 通讯作者: 申惠媛

Functional cross-talk between Rab14 and Rab4 through a dual effector, RUFY1/Rabip4.

• DOI: 10.1091/mbc.e10-01-0074
• 发表时间: 2010-08-01
• 期刊: Molecular biology of the cell
• 影响因子: 3.3
• 作者: Yamamoto H;Koga H;Katoh Y;Takahashi S;Nakayama K;Shin HW
• 通讯作者: Shin HW

Three Homologous ArfGAPs Participate in Coat Protein I-mediated Transport*

• DOI: 10.1074/jbc.m900749200
• 发表时间: 2009-05
• 期刊: Journal of Biological Chemistry
• 影响因子: 4.8
• 作者: Akina Saitoh;Hye-Won Shin;A. Yamada;S. Waguri;K. Nakayama

Arfaptins Are Localized to the trans-Golgi by Interaction with Arl1, but Not Arfs

• DOI: 10.1074/jbc.m110.201442
• 发表时间: 2011-04-01
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Man, Zhiqiu;Kondo, Yumika;Shin, Hye-Won
• 通讯作者: Shin, Hye-Won

Small GTPase ARF3 is involved in lysosomal degradation pathway.

小 GTP 酶 ARF3 参与溶酶体降解途径。

• 发表时间: 2009
• 作者: 福村和宏;谷口一郎;坂本博;大野睦人;井上邦夫;Hye-Won Shin
• 通讯作者: Hye-Won Shin