The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogenic and stress signals to control growth and metabolism. Activation of mTORC1 by amino acids and growth factors involves recruitment of the complex to the lysosomal membrane and is further supported by lysosome distribution to the cell periphery. Here, we show that translocation of lysosomes toward the cell periphery brings mTORC1 into proximity with focal adhesions (FAs). We demonstrate that FAs constitute discrete plasma membrane hubs mediating growth factor signaling and amino acid input into the cell. FAs, as well as the translocation of lysosome-bound mTORC1 to their vicinity, contribute to both peripheral and intracellular mTORC1 activity. Conversely, lysosomal distribution to the cell periphery is dispensable for the activation of mTORC1 constitutively targeted to FAs. This study advances our understanding of spatial mTORC1 regulation by demonstrating that the localization of mTORC1 to FAs is both necessary and sufficient for its activation by growth-promoting stimuli.

中文翻译：

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mTORC1活性通过与粘着斑的空间关联得到支持。

雷帕霉素复合物1（mTORC1）的哺乳动物目标整合有丝分裂和应激信号，以控制生长和代谢。氨基酸和生长因子对mTORC1的激活涉及将复合物募集到溶酶体膜，并由溶酶体分布到细胞周围进一步支持。在这里，我们表明溶酶体向细胞外围的易位使mTORC1与粘着斑（FAs）接近。我们证明FAs构成离散的质膜集线器，介导生长因子信号传导和氨基酸输入到细胞中。FA以及溶酶体结合的mTORC1易位至其附近，有助于外周和细胞内mTORC1活性。相反，溶酶体分布到细胞周围对于组成型靶向FAs的mTORC1的激活是必不可少的。