title: Efficient Tor signaling requires a functional class C Vps protein complex in Saccharomyces cerevisiae.
abstract: The Tor kinases regulate responses to nutrients and control cell growth. Unlike most organisms that only contain one Tor protein, Saccharomyces cerevisiae expresses two, Tor1 and Tor2, which are thought to share all of the rapamycin-sensitive functions attributable to Tor signaling. Here we conducted a genetic screen that defined the global TOR1 synthetic fitness or lethal interaction gene network. This screen identified mutations in distinctive functional categories that impaired vacuolar function, including components of the EGO/Gse and PAS complexes that reduce fitness. In addition, tor1 is lethal in combination with mutations in class C Vps complex components. We find that Tor1 does not regulate the known function of the class C Vps complex in protein sorting. Instead class C vps mutants fail to recover from rapamycin-induced growth arrest or to survive nitrogen starvation and have low levels of amino acids. Remarkably, addition of glutamate or glutamine restores viability to a tor1 pep3 mutant strain. We conclude that Tor1 is more effective than Tor2 at providing rapamycin-sensitive Tor signaling under conditions of amino acid limitation, and that an intact class C Vps complex is required to mediate intracellular amino acid homeostasis for efficient Tor signaling.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Zurita-Martinez
authors.forename: Rekha
authors.initials: R
authors.lastname: Puria
authors.forename: Xuewen
authors.initials: X
authors.lastname: Pan
authors.forename: Jef D
authors.initials: JD
authors.lastname: Boeke
authors.forename: Maria E
authors.initials: ME
authors.lastname: Cardenas
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000596:Amino Acids / Q000494:pharmacology; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D005800:Genes, Fungal; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D033921:Vesicular Transport Proteins
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000596:Amino Acids; D018797:Cell Cycle Proteins; D017931:DNA Primers; D004271:DNA, Fungal; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C071657:PEP3 protein, S cerevisiae; C065710:PEP5 protein, S cerevisiae; C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae; C500749:target of rapamycin protein, S cerevisiae