Leucyl-tRNA synthetase controls TORC1 via the EGO complex
- PMID: 22424774
- DOI: 10.1016/j.molcel.2012.02.009
Leucyl-tRNA synthetase controls TORC1 via the EGO complex
Abstract
The target of rapamycin complex 1 (TORC1) is an essential regulator of eukaryotic cell growth that responds to growth factors, energy levels, and amino acids. The mechanisms through which the preeminent amino acid leucine signals to the TORC1-regulatory Rag GTPases, which activate TORC1 within the yeast EGO complex (EGOC) or the structurally related mammalian Rag-Ragulator complex, remain elusive. We find that the leucyl-tRNA synthetase (LeuRS) Cdc60 interacts with the Rag GTPase Gtr1 of the EGOC in a leucine-dependent manner. This interaction is necessary and sufficient to mediate leucine signaling to TORC1 and is disrupted by the engagement of Cdc60 in editing mischarged tRNA(Leu). Thus, the EGOC-TORC1 signaling module samples, via the LeuRS-intrinsic editing domain, the fidelity of tRNA(Leu) aminoacylation as a proxy for leucine availability.
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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