TSC复合体的空间控制集成了mTORC1在溶酶体中的胰岛素和营养调节
Suchithra Menon1, Christian C Dibble2, George Talbott1
1Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Cell
|February 18, 2014
概括
胰岛素信号通过调节TSC复合体来控制细胞生长.
科学领域:
- 细胞生物学 细胞生物学
- 分子信号传递是分子信号传递.
- 代谢调节 代谢调节 代谢调节
背景情况:
- 拉巴胺素复合体1 (mTORC1) 途径的机械性标调节细胞生长.
- 胰岛素通过PI3K-Akt通路激活mtORC1,抑制TSC复合体以激活Rheb.
- 营养感应和生长因子通路与mTORC1调节的整合仍然不清楚.
研究的目的:
- 阐明胰岛素信号与营养感应通路集成的机制,以控制mTORC1.1.
- 调查TSC复杂局部化在mTORC1激活中的作用.
主要方法:
- 对TSC复合体,Rheb和mtORC1.1.的细胞局部化研究.
- 对TSC2.2的Akt介导酸化的分析.
- 研究PTEN功能丧失对mTORC1信号传输的影响.
主要成果:
- 胰岛素诱导TSC复合物与溶解体表面的急性解离.
- 该TSC复合体以Rheb-依赖的方式与溶解体结合.
- 在胰岛素刺激后,TSC复合物的解离需要通过Akt介导的TSC2酸化.
- 失去PTEN导致通过Akt-依赖TSC复合体解离的构成性mtORC1激活.
结论:
- TSC复合体的空间招募和mTORC1到溶酶体的Rheb整合了多样化的生长信号.
- 这为mTORC1通过胰岛素和营养素的可用性进行调节提供了一个统一的机制.
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