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Scientific article
Open access
English

The Vam6 GEF controls TORC1 by activating the EGO complex

Published inMolecular cell, vol. 35, no. 5, p. 563-573
Publication date2009
Abstract

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) Gtr1(GTP), which interacted strongly with TORC1, rendered TORC1 partially resistant to leucine deprivation, whereas expression of a growth inhibitory, GDP-bound Gtr1(GDP), 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.

Keywords
  • Adaptor Proteins, Vesicular Transport/genetics/metabolism
  • Amino Acid Transport Systems/metabolism
  • Amino Acids/metabolism
  • Cycloheximide/pharmacology
  • DNA-Binding Proteins/metabolism
  • Endosomes/enzymology
  • Guanine Nucleotide Exchange Factors/genetics/metabolism
  • Guanosine Diphosphate/metabolism
  • Guanosine Triphosphate/metabolism
  • Intracellular Membranes/drug effects/enzymology
  • Monomeric GTP-Binding Proteins/genetics/metabolism
  • Multiprotein Complexes
  • Mutation
  • Protein Binding
  • Protein Synthesis Inhibitors/pharmacology
  • Protein Transport
  • Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism
  • Saccharomyces cerevisiae/drug effects/enzymology/genetics/growth & development
  • Saccharomyces cerevisiae Proteins/antagonists & inhibitors/genetics/metabolism
  • Signal Transduction
  • Sirolimus/pharmacology
  • Time Factors
  • Transcription Factors/metabolism
  • Vacuoles/drug effects/enzymology
Citation (ISO format)
BINDA, Matteo et al. The Vam6 GEF controls TORC1 by activating the EGO complex. In: Molecular cell, 2009, vol. 35, n° 5, p. 563–573. doi: 10.1016/j.molcel.2009.06.033
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal1097-4164
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416downloads

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