Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway
- PMID: 22424946
- DOI: 10.1016/j.cell.2012.02.044
Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway
Abstract
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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Comment in
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Hijacking leucyl-tRNA synthetase for amino acid-dependent regulation of TORC1.Mol Cell. 2012 Apr 13;46(1):4-6. doi: 10.1016/j.molcel.2012.03.028. Mol Cell. 2012. PMID: 22500735 Free PMC article.
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