近日，加拿大多伦多大学Anne-Claude Gingras团队发现，GATOR–Rag GTPase途径通过溶酶体衍生的氨基酸抑制mTORC1活化。2020年10月16日，《科学》发表了这一成果。

Title: The GATOR–Rag GTPase pathway inhibits mTORC1 activation by lysosome-derived amino acids

Author: Geoffrey G. Hesketh, Fotini Papazotos, Judy Pawling, Dushyandi Rajendran, James D. R. Knight, Sebastien Martinez, Mikko Taipale, Daniel Schramek, James W. Dennis, Anne-Claude Gingras

Issue&Volume: 2020/10/16

Abstract: The mechanistic target of rapamycin complex 1 (mTORC1) couples nutrient sufficiency to cell growth. mTORC1 is activated by exogenously acquired amino acids sensed through the GATOR–Rag guanosine triphosphatase (GTPase) pathway, or by amino acids derived through lysosomal degradation of protein by a poorly defined mechanism. Here, we revealed that amino acids derived from the degradation of protein (acquired through oncogenic Ras-driven macropinocytosis) activate mTORC1 by a Rag GTPase–independent mechanism. mTORC1 stimulation through this pathway required the HOPS complex and was negatively regulated by activation of the GATOR-Rag GTPase pathway. Therefore, distinct but functionally coordinated pathways control mTORC1 activity on late endocytic organelles in response to distinct sources of amino acids.

DOI: 10.1126/science.aaz0863

Source: https://science.sciencemag.org/content/370/6514/351