Leucyl-tRNA Synthetase Controls TORC1 via the EGO Complex

Mol Cell. 2012 Apr 13;46(1):105-10. doi: 10.1016/j.molcel.2012.02.009. Epub 2012 Mar 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Leucine / genetics
  • Leucine / metabolism*
  • Leucine-tRNA Ligase / genetics
  • Leucine-tRNA Ligase / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Saccharomyces cerevisiae Proteins
  • TORC1 protein complex, S cerevisiae
  • Transcription Factors
  • Leucine-tRNA Ligase
  • Leucine