Abstract
Abstract Osmoregulation, i.e. the active control of the cellular water balance, encompasses homeostatic mechanisms crucial for life. The osmoregulatory system in the yeast Saccharomyces cerevisiae is particularly well understood, although many details of the regulatory mechanisms still remain to be discovered. Central to yeast osmoregulation is the high osmolarity glycerol (HOG) signalling network, a branched mitogen-activated protein kinase (MAPK) pathway that converges on the MAPK Hog1. Active Hog1 controls numerous cellular processes in the cytosol (cell cycle, translation, ion, water and glycerol transport and central metabolism) as well as the expression of numerous genes. In order to achieve a quantitative understanding and to fit different processes in a temporal order, we have generated a comprehensive mathematical model of yeast osmoregulation in collaboration with theoreticians. Using model simulation and quantitative time-course experimentation, we have analysed mechanisms of feedback control of the HOG pathway. These studies illustrate how a signalling pathway combines rigorous feedback control with maintenance of signalling competence, as required for a system controlling cell homeostasis.
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