Rheb and Rags come together at the lysosome to activate mTORC1
Rheb and Rags come together at the lysosome to activate mTORC1
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DOI：
10.1042/bst20130037
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发表时间：
2013-08-01
影响因子：
3.9
通讯作者：
Zwartkruis, Fried J. T.
中科院分区：
文献类型：
--
作者：
Groenewoud, Marlous J.;Zwartkruis, Fried J. T.
雷帕霉素复合体1的哺乳动物靶点mTORC1是一种高度保守的蛋白质复合体，通过其激酶mTOR调节细胞的生长和代谢。MTOR的活性受多种GTP酶的控制，其中Rheb和RAGS起着核心作用。氨基酸的存在是mTORC1活性的严格要求。异源二聚体RAG GTP酶通过与溶酶体激活剂复合体的氨基酸依赖相互作用将mTORC1定位于溶酶体。Rheb也被认为存在于溶酶体上，以激活mTORC1。Rheb对生长因子有反应，但与PLD1(磷脂酶D1)一起，也是刺激mTORC1对氨基酸做出反应的机制的组成部分。在这篇文章中，我们简要概述了氨基酸影响RAG功能的新机制。在现有文献的基础上，我们假设Rheb在高尔基体被激活，它将从那里进入溶酶体。可能需要将内体成熟为溶酶体，以确保持续供应GTP结合的Rheb以激活mTORC1，这可能有助于推动成熟过程。
mTORC1 (mammalian target of rampamycin complex 1) is a highly conserved protein complex regulating cell growth and metabolism via its kinase mTOR (mammalian target of rapamycin). The activity of mTOR is under the control of various GTPases, of which Rheb and the Rags play a central role. The presence of amino acids is a strict requirement for mTORC1 activity. The heterodimeric Rag GTPases localize mTORC1 to lysosomes by their amino-acid-dependent interaction with the lysosomal Ragulator complex. Rheb is also thought to reside on lysosomes to activate mTORC1. Rheb is responsive to growth factors, but, in conjunction with PLD1 (phospholipase D1), is also an integral part of the machinery that stimulates mTORC1 in response to amino acids. In the present article, we provide a brief overview of novel mechanisms by which amino acids affect the function of Rags. On the basis of existing literature, we postulate that Rheb is activated at the Golgi from where it will travel to lysosomes. Maturation of endosomes into lysosomes may be required to assure a continuous supply of GTP-bound Rheb for mTORC1 activation, which may help to drive the maturation process.