title: 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.
authors.affiliation: Department of Biology, Division of Biochemistry, University of Fribourg, CH-1700 Fribourg, Switzerland.
authors.forename: Grégory
authors.initials: G
authors.lastname: Bonfils
authors.forename: Malika
authors.initials: M
authors.lastname: Jaquenoud
authors.forename: Séverine
authors.initials: S
authors.lastname: Bontron
authors.forename: Clemens
authors.initials: C
authors.lastname: Ostrowicz
authors.forename: Christian
authors.initials: C
authors.lastname: Ungermann
authors.forename: Claudio
authors.initials: C
authors.lastname: De Virgilio
mesh_terms: D007930:Leucine / Q000235:genetics / Q000378:metabolism*; D007935:Leucine-tRNA Ligase / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; D007935:Leucine-tRNA Ligase; D007930:Leucine