Search for novel membrane trafficking pathway involved in autophagy

寻找参与自噬的新型膜运输途径

• 批准号: 23770216
• 负责人: ITOH Takashi
• 金额: $ 2.91万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23770216/
• 关键词: タンパク質分解; 膜輸送; オートファジー; Rab; Rab-GAP

Macroautpohagy (referred to as autophagy hereafter) accompanies dynamic membrane remodeling such as autophagosome formation and fusion between autophagosome and lysosome. However, the regulation of such membrane remodeling is largely unknown. Since I had identified three Rab-GAPs, inactivators of Rab-type small GTPases, as autophagosome resident proteins, here I addressed the function of these Rab-GAPs (OATL1/TBC1D25, TBC1D2B, TBC1D11) in autophagy. They were localized at autophagosomes and bound with LC3, an autophagosome resident protein used as a marker of autophagosome. TBC1D2B and TBC1D25 required the interaction with LC3 for their localization at autophagosomes, since a point mutation that abolished the interaction impaired their localization. Although I previously revealed that overexpression of TBC1D25 inhibits fusion between autophagosomes and lysosomes, overexpression of TBC1D2B nor TBC1D11 did not inhibit any process of autophagy.These results so far did not clarify relationship between these Rab-GAPs and autophagy. However, I suppose that it is possible that LC3 acts as a scaffold for Rab-GAPs and has a role in membrane trafficking in addition to in autophagy.

巨噬（以下简称自噬）伴随着动态的膜重塑，如自噬体的形成以及自噬体与溶酶体的融合。然而，这种膜重塑的调控在很大程度上是未知的。由于我已经确定了三种lab - gap，即lab型小gtpase的失活因子，作为自噬体的驻留蛋白，在这里我讨论了这些lab - gap （OATL1/TBC1D25, TBC1D2B, TBC1D11）在自噬中的功能。它们定位于自噬体，并与LC3结合，LC3是一种自噬体驻留蛋白，被用作自噬体的标志物。TBC1D2B和TBC1D25需要与LC3相互作用才能在自噬体上定位，因为取消相互作用的点突变损害了它们的定位。虽然我之前发现过表达TBC1D25抑制自噬体和溶酶体之间的融合，但过表达TBC1D2B和TBC1D11并没有抑制任何自噬过程。到目前为止，这些结果还没有明确这些rab - gap与自噬之间的关系。然而，我认为LC3可能作为rab - gap的支架，除了在自噬中起作用外，还在膜运输中起作用。

项目成果

オートファジーに関わるRab不活性化因子の探索

寻找参与自噬的Rab失活因子

• 发表时间: 2011
• 作者: Itoh;T.;Fujita;N.;Saitoh;T.;Komatsu;M;Akira;S.;Yoshimori;T.;and Fukuda;M.;伊藤敬
• 通讯作者: 伊藤敬

Functional Analysis of Rab33B in Autophagy

Rab33B 在自噬中的功能分析

• 发表时间: 2011
• 作者: Itoh;T.
• 通讯作者: T.

A possible regulation of Rab33B-dependent membrane trafficking by the Atg12-5/16L1 complex

Atg12-5/16L1 复合物对 Rab33B 依赖性膜运输的可能调节

• 发表时间: 2012
• 作者: Itoh;T.;Fujita;N.;Saitoh;T.;Komatsu;M;Akira;S.;Yoshimori;T.;and Fukuda;M.
• 通讯作者: M.

A possible regulation of Rab33B-dependent membrane trafficking by the Atg12-5/16L1 complex.

Atg12-5/16L1 复合物对 Rab33B 依赖性膜运输的可能调节。

• 发表时间: 2012
• 作者: Itoh;T.;Fujita;N.;Saitoh;T.;Komatsu;M;Akira;S.;Yoshimori;T.;and Fukuda;M.
• 通讯作者: M.

Small GTPase Rab12 Regulates Constitutive Degradation of Transferrin Receptor

• DOI: 10.1111/j.1600-0854.2011.01240.x
• 发表时间: 2011-10-01
• 期刊: TRAFFIC
• 影响因子: 4.5
• 作者: Matsui, Takahide;Itoh, Takashi;Fukuda, Mitsunori
• 通讯作者: Fukuda, Mitsunori