TOR and RAS pathways regulate desiccation tolerance in Saccharomyces cerevisiae

Mol Biol Cell. 2013 Jan;24(2):115-28. doi: 10.1091/mbc.E12-07-0524. Epub 2012 Nov 21.

Abstract

Tolerance to desiccation in cultures of Saccharomyces cerevisiae is inducible; only one in a million cells from an exponential culture survive desiccation compared with one in five cells in stationary phase. Here we exploit the desiccation sensitivity of exponentially dividing cells to understand the stresses imposed by desiccation and their stress response pathways. We found that induction of desiccation tolerance is cell autonomous and that there is an inverse correlation between desiccation tolerance and growth rate in glucose-, ammonia-, or phosphate-limited continuous cultures. A transient heat shock induces a 5000-fold increase in desiccation tolerance, whereas hyper-ionic, -reductive, -oxidative, or -osmotic stress induced much less. Furthermore, we provide evidence that the Sch9p-regulated branch of the TOR and Ras-cAMP pathway inhibits desiccation tolerance by inhibiting the stress response transcription factors Gis1p, Msn2p, and Msn4p and by activating Sfp1p, a ribosome biogenesis transcription factor. Among 41 mutants defective in ribosome biogenesis, a subset defective in 60S showed a dramatic increase in desiccation tolerance independent of growth rate. We suggest that reduction of a specific intermediate in 60S biogenesis, resulting from conditions such as heat shock and nutrient deprivation, increases desiccation tolerance.

Publication types

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

MeSH terms

  • Adaptation, Physiological
  • Culture Media
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dehydration
  • Gene Knockout Techniques
  • Phosphatidylinositol 3-Kinases / metabolism
  • Ribosome Subunits, Large, Eukaryotic / metabolism
  • Saccharomyces cerevisiae / growth & development*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / antagonists & inhibitors
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Sirolimus / pharmacology
  • Stress, Physiological
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism*
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • Culture Media
  • Saccharomyces cerevisiae Proteins
  • TORC1 protein complex, S cerevisiae
  • Transcription Factors
  • TOR1 protein, S cerevisiae
  • Cyclic AMP-Dependent Protein Kinases
  • RAS1 protein, S cerevisiae
  • RAS2 protein, S cerevisiae
  • ras Proteins
  • Sirolimus