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The Vam6 GEF controls TORC1 by activating the EGO complex

  • Binda, Matteo Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
  • Péli-Gulli, Marie-Pierre Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
  • Bonfils, Grégory Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
  • Panchaud, Nicolas Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
  • Urban, Jörg Department of Molecular Biology, University of Geneva, Switzerland
  • Sturgill, Thomas W. Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville, USA
  • Loewith, Robbie Department of Molecular Biology, University of Geneva, Switzerland
  • De Virgilio, Claudio Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
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    11.09.2009
Published in:
  • Molecular Cell. - 2009, vol. 35, no. 5, p. 563-573
English The target of rapamycin complex 1 (TORC1) is a central regulator of eukaryotic cell growth that is activated by a variety of hormones (e.g., insulin) and nutrients (e.g., amino acids) and is deregulated in various cancers. Here, we report that the yeast Rag GTPase homolog Gtr1, a component of the vacuolar-membrane-associated EGO complex (EGOC), interacts with and activates TORC1 in an amino-acid-sensitive manner. Expression of a constitutively active (GTP-bound) Gtr1GTP, which interacted strongly with TORC1, rendered TORC1 partially resistant to leucine deprivation, whereas expression of a growth inhibitory, GDP-bound Gtr1GDP, caused constitutively low TORC1 activity. We also show that the nucleotide-binding status of Gtr1 is regulated by the conserved guanine nucleotide exchange factor (GEF) Vam6. Thus, in addition to its regulatory role in homotypic vacuolar fusion and vacuole protein sorting within the HOPS complex, Vam6 also controls TORC1 function by activating the Gtr1 subunit of the EGO complex.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/301365
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