The high-osmolarity glycerol- and cell wall integrity-MAP kinase pathways of Saccharomyces cerevisiae are involved in adaptation to the action of killer toxin HM-1

Yeast. 2012 Nov;29(11):475-85. doi: 10.1002/yea.2927. Epub 2012 Oct 15.


Fps1p is an aquaglyceroporin important for turgor regulation of Saccharomyces cerevisiae. Previously we reported the involvement of Fps1p in the yeast-killing action of killer toxin HM-1. The fps1 cells showed a high HM-1-resistant phenotype in hypotonic medium and an HM-1-susceptible phenotype in hypertonic medium. This osmotic dependency in HM-1 susceptibility was similar to those observed in Congo red, but different from those observed in other cell wall-disturbing agents. These results indicate that HM-1 exerts fungicidal activity mainly by binding and inserting into the yeast cell wall structure, rather than by inhibiting 1,3-β-glucan synthase. We next determined HM-1-susceptibility and diphospho-MAP kinase inductions in S. cerevisiae. In the wild-type cell, expressions of diphospho-Hog1p and -Slt2p, and mRNA transcription of CWP1 and HOR2, were induced within 1 h after an addition of HM-1. ssk1 and pbs2 cells, but not sho1 and hkr1 cells, showed HM-1-sensitive phenotypes and lacked inductions of phospho-Hog1p in response to HM-1. mid2, rom2 and bck1 cells showed HM-1-sensitive phenotypes and decreased inductions of phospho-Slt2p in response to HM-1. From these results, we postulated that the Sln1-Ypd1-Ssk1 branch of the high-osmolality glycerol (HOG) pathway and plasma membrane sensors of the cell wall integrity (CWI) pathway detect cell wall stresses caused by HM-1. We further suggested that activations of both HOG and CWI pathways have an important role in the adaptive response to HM-1 toxicity.

MeSH terms

  • Cell Wall / drug effects
  • Culture Media / chemistry
  • Glycerol / metabolism
  • Killer Factors, Yeast / toxicity*
  • Mitogen-Activated Protein Kinases / metabolism
  • Osmotic Pressure*
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction*
  • Stress, Physiological*


  • Culture Media
  • Killer Factors, Yeast
  • Saccharomyces cerevisiae Proteins
  • Mitogen-Activated Protein Kinases
  • Glycerol