Efficient Tor signaling requires a functional class C Vps protein complex in Saccharomyces cerevisiae

Genetics. 2007 Aug;176(4):2139-50. doi: 10.1534/genetics.107.072835. Epub 2007 Jun 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport
  • Amino Acids / pharmacology
  • Base Sequence
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA Primers / genetics
  • DNA, Fungal / genetics
  • Genes, Fungal
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Multiprotein Complexes
  • Mutation
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Protein Serine-Threonine Kinases
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / classification
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Vesicular Transport Proteins

Substances

  • Adaptor Proteins, Vesicular Transport
  • Amino Acids
  • Cell Cycle Proteins
  • DNA Primers
  • DNA, Fungal
  • Membrane Proteins
  • Multiprotein Complexes
  • PEP3 protein, S cerevisiae
  • PEP5 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Vesicular Transport Proteins
  • Phosphotransferases (Alcohol Group Acceptor)
  • TOR1 protein, S cerevisiae
  • TOR2 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • target of rapamycin protein, S cerevisiae