title: Systems Level Analysis of the Yeast Osmo-Stat.
abstract: Adaptation is an important property of living organisms enabling them to cope with environmental stress and maintaining homeostasis. Adaptation is mediated by signaling pathways responding to different stimuli. Those signaling pathways might communicate in order to orchestrate the cellular response to multiple simultaneous stimuli, a phenomenon called crosstalk. Here, we investigate possible mechanisms of crosstalk between the High Osmolarity Glycerol (HOG) and the Cell Wall Integrity (CWI) pathways in yeast, which mediate adaptation to hyper- and hypo-osmotic challenges, respectively. We combine ensemble modeling with experimental investigations to test in quantitative terms different hypotheses about the crosstalk of the HOG and the CWI pathways. Our analyses indicate that for the conditions studied i) the CWI pathway activation employs an adaptive mechanism with a variable volume-dependent threshold, in contrast to the HOG pathway, whose activation relies on a fixed volume-dependent threshold, ii) there is no or little direct crosstalk between the HOG and CWI pathways, and iii) its mainly the HOG alone mediating adaptation of cellular osmotic pressure for both hyper- as well as hypo-osmotic stress. Thus, by iteratively combining mathematical modeling with experimentation we achieved a better understanding of regulatory mechanisms of yeast osmo-homeostasis and formulated new hypotheses about osmo-sensing.
authors: Institut für Experimentelle Innere Medizin, Medizinische Fakultät, Otto-von-Guericke-Universität, Magdeburg, Germany.|Division of Theoretical Systems Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Soheil Rastgou
authors: SR
authors: Talemi
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Göteborg, Sweden.
authors: Carl-Fredrik
authors: CF
authors: Tiger
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Göteborg, Sweden.
authors: Mikael
authors: M
authors: Andersson
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Göteborg, Sweden.
authors: Roja
authors: R
authors: Babazadeh
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Göteborg, Sweden.
authors: Niek
authors: N
authors: Welkenhuysen
authors: Theoretical Biophysics, Humboldt Universität zu Berlin, Berlin, Germany.
authors: Edda
authors: E
authors: Klipp
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Göteborg, Sweden.|Department of Biology and Biological Engineering, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
authors: Stefan
authors: S
authors: Hohmann
authors: Institut für Experimentelle Innere Medizin, Medizinische Fakultät, Otto-von-Guericke-Universität, Magdeburg, Germany.
authors: Jörg
authors: J
authors: Schaber
mesh_terms: D000222:Adaptation, Physiological; D002473:Cell Wall / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005990:Glycerol / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D009997:Osmotic Pressure; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D005990:Glycerol