A model-based study delineating the roles of the two signaling branches of Saccharomyces cerevisiae, Sho1 and Sln1, during adaptation to osmotic stress.
Adaptation to osmotic shock in Saccharomyces cerevisiae is brought about by the activation of two independent signaling pathways, Sho1 and Sln1, which in turn trigger the high osmolarity glycerol (HOG) pathway. The HOG pathway thereby activates the transcription of Gpd1p, an enzyme necessary to synthesize glycerol. The production of glycerol brings about a change in the intracellular osmolarity leading to adaptation. We present a detailed mechanistic model for the response of the yeast to hyperosmotic shock. The model integrates the two branches, Sho1 and Sln1, of the HOG pathway and also includes the mitogen-activated protein kinase cascade, gene regulation and metabolism. Model simulations are consistent with known experimental results for wild-type strain, and Ste11Delta and Ssk1Delta mutant strains subjected to osmotic stress. Simulation results predict that both the branches contribute to the overall wild-type response for moderate osmotic shock, while under severe osmotic shock, the cell responds mainly through the Sln1 branch. The analysis shows that the Sln1 branch helps the cell in preventing cross-talk to other signaling pathways by inhibiting ste11ste50 activation and also by increasing the phosphorylation of Ste50. We show that the negative feedbacks to the Sho1 branch must be faster than those to the Sln1 branch to simultaneously achieve pathway specificity and adaptation during hyperosmotic shock. Sensitivity analysis revealed that the presence of both branches imparts robust behavior to the cell under osmoadaptation to perturbations.
Parmar
J H
JH
Department of Chemical Engineering, Indian Institute of Technology, Bombay, Powai, Mumbai 400076, India.
Bhartiya
Sharad
S
Venkatesh
K V
KV
D000222:Adaptation, Physiological; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D008954:Models, Biological; D009997:Osmotic Pressure; D011494:Protein Kinases / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D015398:Signal Transduction
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C459787:SHO1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C083749:SLN1 protein, S cerevisiae