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.

Osmolyte homeostasis controls single-cell growth rate and maximum cell size ofSaccharomyces cerevisiae

“…Obviously, hypoosmotic shock results in a short overshoot of cell size (Fig. 6C), as previously reported in (37). Hyperosmotic shock exclusively leads to elastic deformation, while hypoosmotic shock leads to negligibly small plastic deformation.…”

“…To our knowledge, this is the first time that the joint-dynamics of Hog1 enrichment versus volume following a hyperosmotic shock (26) could be reproduced and explained by a mathematical model. Additionally, our model can describe the response to hypoosmotic shock similarly to previous reports (37). The simulations illustrate the functionality of the coupled model over a wide range of cell sizes.…”

Correlating single-molecule characteristics of the yeast aquaglyceroporin Fps1 with environmental perturbations directly in living cells

“…Biochemical studies suggest that increased external osmolarity causes rapid Fps1 closure, whereas decreased osmolarity results in the channel opening 30,52,53 . To determine how hyper-osmotic conditions affect Fps1 architecture, we grew the cells in 1M sorbitol to reach complete osmoadaptation ( Fig.…”

Yeast two‐ and three‐species hybrids and high‐sugar fermentation

“…The overall cell volume is also reduced, and the yeast cells have to adapt their internal osmolarity to the hyperosmotic external conditions to restore the optimal cell volume (e.g. Pratt et al, 2003;Munna et al, 2015;Talemi et al, 2016).…”