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The Vam6 GEF controls TORC1 by activating the EGO complex

Binda, Matteo
Péli-Gulli, Marie-Pierre
Bonfils, Grégory
Panchaud, Nicolas
Sturgill, Thomas W
Published in Molecular cell. 2009, vol. 35, no. 5, p. 563-73
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/metabolismAmino Acid Transport Systems/metabolismAmino Acids/metabolismCycloheximide/pharmacologyDNA-Binding Proteins/metabolismEndosomes/enzymologyGuanine Nucleotide Exchange Factors/genetics/metabolismGuanosine Diphosphate/metabolismGuanosine Triphosphate/metabolismIntracellular Membranes/drug effects/enzymologyMonomeric GTP-Binding Proteins/genetics/metabolismMultiprotein ComplexesMutationProtein BindingProtein Synthesis Inhibitors/pharmacologyProtein TransportProtein-Serine-Threonine Kinases/antagonists & inhibitors/metabolismSaccharomyces cerevisiae/drug effects/enzymology/genetics/growth & developmentSaccharomyces cerevisiae Proteins/antagonists & inhibitors/genetics/metabolismSignal TransductionSirolimus/pharmacologyTime FactorsTranscription Factors/metabolismVacuoles/drug effects/enzymology
PMID: 19748353
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BINDA, Matteo et al. The Vam6 GEF controls TORC1 by activating the EGO complex. In: Molecular cell, 2009, vol. 35, n° 5, p. 563-73. https://archive-ouverte.unige.ch/unige:18219

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Deposited on : 2012-01-30

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