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Nature:mTOR的一个溶酶体氨基酸感应物

摘要 : “mTORC1蛋白激酶复合物”将营养成分和生长刺激相结合来调制那些调控细胞代谢和生理的信号作用通道。Giulio Superti-Furga及同事发现,人类的 “溶质载体蛋白群”的一个成员SLC38A9是能够直接感应氨基酸和激活mTORC1的溶酶体机制的一个有机组成部分。

“mTORC1蛋白激酶复合物”将营养成分和生长刺激相结合来调制那些调控细胞代谢和生理的信号作用通道。虽然氨基酸对于mTORC1活性是必不可少的,但溶酶体上的氨基酸感应机制的分子性质却不知道。

在这项研究中,Giulio Superti-Furga及同事发现,人类的 “溶质载体蛋白群”的一个成员SLC38A9是能够直接感应氨基酸和激活mTORC1的溶酶体机制的一个有机组成部分。

原文链接:SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1

Cell growth and proliferation are tightly linked to nutrient availability. The mechanistic target of rapamycin complex 1 (mTORC1) integrates the presence of growth factors, energy levels, glucose and amino acids to modulate metabolic status and cellular responses1, 2, 3. mTORC1 is activated at the surface of lysosomes by the RAG GTPases and the Ragulator complex through a not fully understood mechanism monitoring amino acid availability in the lysosomal lumen and involving the vacuolar H+-ATPase4, 5, 6, 7, 8. Here we describe the uncharacterized human member 9 of the solute carrier family 38 (SLC38A9) as a lysosomal membrane-resident protein competent in amino acid transport. Extensive functional proteomic analysis established SLC38A9 as an integral part of the Ragulator–RAG GTPases machinery. Gain of SLC38A9 function rendered cells resistant to amino acid withdrawal, wheras loss of SLC38A9 expression impaired amino-acid-induced mTORC1 activation. Thus SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR. 

对应Nature杂志: 2015年03月26日Nature杂志精选

来源: Nature 浏览次数:10

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