The Vam6 GEF Controls TORC1 by Activating the EGO Complex
Copyright policy )The Vam6 GEF Controls TORC1 by Activating the EGO Complex
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.
- University of Virginia United States
- RERO - Library Network of Western Switzerland Switzerland
- University of Geneva Switzerland
- University of Fribourg Switzerland
570, Time Factors, Saccharomyces cerevisiae Proteins, Amino Acid Transport Systems, Adaptor Proteins, Vesicular Transport/genetics/metabolism, Amino Acids/metabolism, Vacuoles/drug effects/enzymology, Endosomes, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, Guanosine Diphosphate, Endosomes/enzymology, Guanine Nucleotide Exchange Factors, Transcription Factors/metabolism, Amino Acids, Cycloheximide, Molecular Biology, Monomeric GTP-Binding Proteins, Protein Synthesis Inhibitors, Saccharomyces cerevisiae Proteins/antagonists & inhibitors/genetics/metabolism, DNA-Binding Proteins/metabolism, Saccharomyces cerevisiae/drug effects/enzymology/genetics/growth & development, Sirolimus/pharmacology, Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism, Cell Biology, Intracellular Membranes, Amino Acid Transport Systems/metabolism, Intracellular Membranes/drug effects/enzymology, Guanine Nucleotide Exchange Factors/genetics/metabolism, DNA-Binding Proteins, Adaptor Proteins, Vesicular Transport, Protein Transport, Monomeric GTP-Binding Proteins/genetics/metabolism, Protein Synthesis Inhibitors/pharmacology, Guanosine Triphosphate/metabolism, Multiprotein Complexes, Mutation, Cycloheximide/pharmacology, Guanosine Diphosphate/metabolism, Guanosine Triphosphate, Protein Binding, Signal Transduction, ddc: ddc:570
570, Time Factors, Saccharomyces cerevisiae Proteins, Amino Acid Transport Systems, Adaptor Proteins, Vesicular Transport/genetics/metabolism, Amino Acids/metabolism, Vacuoles/drug effects/enzymology, Endosomes, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, Guanosine Diphosphate, Endosomes/enzymology, Guanine Nucleotide Exchange Factors, Transcription Factors/metabolism, Amino Acids, Cycloheximide, Molecular Biology, Monomeric GTP-Binding Proteins, Protein Synthesis Inhibitors, Saccharomyces cerevisiae Proteins/antagonists & inhibitors/genetics/metabolism, DNA-Binding Proteins/metabolism, Saccharomyces cerevisiae/drug effects/enzymology/genetics/growth & development, Sirolimus/pharmacology, Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism, Cell Biology, Intracellular Membranes, Amino Acid Transport Systems/metabolism, Intracellular Membranes/drug effects/enzymology, Guanine Nucleotide Exchange Factors/genetics/metabolism, DNA-Binding Proteins, Adaptor Proteins, Vesicular Transport, Protein Transport, Monomeric GTP-Binding Proteins/genetics/metabolism, Protein Synthesis Inhibitors/pharmacology, Guanosine Triphosphate/metabolism, Multiprotein Complexes, Mutation, Cycloheximide/pharmacology, Guanosine Diphosphate/metabolism, Guanosine Triphosphate, Protein Binding, Signal Transduction, ddc: ddc:570
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