The mTORC1 kinase is a master growth regulator that senses many environmental cues, including amino acids. Activation of mTORC1 by arginine requires SLC38A9, a poorly understood lysosomal membrane protein with homology to amino acid transporters. Here, we validate that SLC38A9 is an arginine sensor for the mTORC1 pathway, and we uncover an unexpectedly central role for SLC38A9 in amino acid homeostasis. SLC38A9 mediates the transport, in an arginine-regulated fashion, of many essential amino acids out of lysosomes, including leucine, which mTORC1 senses through the cytosolic Sestrin proteins. SLC38A9 is necessary for leucine generated via lysosomal proteolysis to exit lysosomes and activate mTORC1. Pancreatic cancer cells, which use macropinocytosed protein as a nutrient source, require SLC38A9 to form tumors. Thus, through SLC38A9, arginine serves as a lysosomal messenger that couples mTORC1 activation to the release from lysosomes of the essential amino acids needed to drive cell growth.

中文翻译：

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从溶酶体中流出必需氨基酸并使用蛋白质作为营养物质时，需要mTORC1激活剂SLC38A9。

mTORC1激酶是一种主要的生长调节剂，可感知许多环境线索，包括氨基酸。精氨酸激活mTORC1需要SLC38A9，这是一种与氨基酸转运蛋白同源的鲜为人知的溶酶体膜蛋白。在这里，我们验证了SLC38A9是mTORC1途径的精氨酸传感器，并且我们发现了SLC38A9在氨基酸稳态中的出乎意料的核心作用。SLC38A9以精氨酸调节的方式介导了许多必需氨基酸从溶酶体中的转运，包括亮氨酸，mTORC1通过溶质中的雌激素蛋白进行感测。SLC38A9对于通过溶酶体蛋白水解产生的亮氨酸排出溶酶体并激活mTORC1是必需的。使用巨胞饮蛋白作为营养来源的胰腺癌细胞需要SLC38A9才能形成肿瘤。因此，通过SLC38A9，