Ragulator-Rag 复合物将 mTORC1 靶向到溶酶体表面，并且对于其被氨基酸激活是必需的。
Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids.
机构信息
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
出版信息
Cell. 2010 Apr 16;141(2):290-303. doi: 10.1016/j.cell.2010.02.024. Epub 2010 Apr 8.
The mTORC1 kinase promotes growth in response to growth factors, energy levels, and amino acids, and its activity is often deregulated in disease. The Rag GTPases interact with mTORC1 and are proposed to activate it in response to amino acids by promoting mTORC1 translocation to a membrane-bound compartment that contains the mTORC1 activator, Rheb. We show that amino acids induce the movement of mTORC1 to lysosomal membranes, where the Rag proteins reside. A complex encoded by the MAPKSP1, ROBLD3, and c11orf59 genes, which we term Ragulator, interacts with the Rag GTPases, recruits them to lysosomes, and is essential for mTORC1 activation. Constitutive targeting of mTORC1 to the lysosomal surface is sufficient to render the mTORC1 pathway amino acid insensitive and independent of Rag and Ragulator, but not Rheb, function. Thus, Rag-Ragulator-mediated translocation of mTORC1 to lysosomal membranes is the key event in amino acid signaling to mTORC1.
mTORC1 激酶可响应生长因子、能量水平和氨基酸促进生长，其活性在疾病中经常失调。Rag GTPases 与 mTORC1 相互作用，并通过促进 mTORC1 易位到包含 mTORC1 激活剂 Rheb 的膜结合隔室来响应氨基酸而被提议激活它。我们表明，氨基酸诱导 mTORC1 向溶酶体膜运动，Rag 蛋白就位于溶酶体膜上。由 MAPKSP1、ROBLD3 和 c11orf59 基因编码的复合物，我们称之为 Ragulator，与 Rag GTPases 相互作用，将它们招募到溶酶体上，并对 mTORC1 的激活至关重要。将 mTORC1 持续靶向溶酶体表面足以使 mTORC1 途径对氨基酸不敏感，并独立于 Rag 和 Ragulator，但不独立于 Rheb 的功能。因此，Rag-Ragulator 介导的 mTORC1 向溶酶体膜的易位是氨基酸信号传递到 mTORC1 的关键事件。
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