Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Dallas, TX 75390-9041, USA.
Mol Cell. 2012 Sep 28;47(6):851-62. doi: 10.1016/j.molcel.2012.08.001. Epub 2012 Sep 6.
Cells continually assess their energy and nutrient state to maintain growth and survival and engage necessary homeostatic mechanisms. Cell-autonomous responses to the fed state require the surveillance of the availability of amino acids and other nutrients. The mammalian target of rapamycin complex 1 (mTORC1) integrates information on nutrient and amino acid availability to support protein synthesis and cell growth. We identify the G protein-coupled receptor (GPCR) T1R1/T1R3 as a direct sensor of the fed state and amino acid availability. Knocking down this receptor, which is found in most tissues, reduces the ability of amino acids to signal to mTORC1. Interfering with this receptor alters localization of mTORC1, downregulates expression of pathway inhibitors, upregulates key amino acid transporters, blocks translation initiation, and induces autophagy. These findings reveal a mechanism for communicating amino acid availability through a GPCR to mTORC1 in mammals.
细胞不断评估其能量和营养状态，以维持生长和存活，并启动必要的体内平衡机制。细胞自主响应进食状态需要监控氨基酸和其他营养物质的可用性。雷帕霉素靶蛋白复合物 1（mTORC1）整合了有关营养和氨基酸可用性的信息，以支持蛋白质合成和细胞生长。我们发现 G 蛋白偶联受体（GPCR）T1R1/T1R3 是进食状态和氨基酸可用性的直接传感器。敲低该受体（在大多数组织中均有表达）会降低氨基酸向 mTORC1 发出信号的能力。干扰该受体可改变 mTORC1 的定位，下调途径抑制剂的表达，上调关键氨基酸转运体，阻断翻译起始，并诱导自噬。这些发现揭示了一种通过 GPCR 将氨基酸可用性传递给哺乳动物中 mTORC1 的机制。
