Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase, which regulates protein translation, cell size, and autophagy. However, the amino acid sensor that directly couples intracellular amino acid-mediated signaling to mTORC1 is unknown. Here we show that leucyl-tRNA synthetase (LRS) plays a critical role in amino acid-induced mTORC1 activation by sensing intracellular leucine concentration and initiating molecular events leading to mTORC1 activation. Mutation of LRS amino acid residues important for leucine binding renders the mTORC1 pathway insensitive to intracellular levels of amino acids. We show that LRS directly binds to Rag GTPase, the mediator of amino acid signaling to mTORC1, in an amino acid-dependent manner and functions as a GTPase-activating protein (GAP) for Rag GTPase to activate mTORC1. This work demonstrates that LRS is a key mediator for amino acid signaling to mTORC1.
SciCrunch is a data sharing and display platform. Anyone can create a custom portal where they can select searchable subsets of hundreds of data sources, brand their web pages and create their community. SciCrunch will push data updates automatically to all portals on a weekly basis. User communities can also add their own data to scicrunch, however this is not currently a free service.