The Dynamical Systems Properties of the HOG Signaling Cascade

Figure 3

Sequential sketch of yeast adaptation to a hyperosmotic shock. The evolution with time of the size, phosphorylation of Hog1p, and internal concentration of glycerol are schematically represented in the center of the picture. (1) After an increase of the external osmolarity (green), a first mechanical response corresponds to a rapid loss of water (blue arrow). It leads to a decrease of the cell size and a loss of turgor pressure. (2) HOG osmosensors (blue) activate the pathway and eventually lead to the phosphorylation of Hog1p. (3) Hog1PP induces several processes: (a) Inactivation of the glycerol channel Fps1p preventing glycerol leakage; (b) direct or indirect activation of cytoplasmic actors, for example, 6-phosphofructo-2-kinase (Pfk2p) involved in glycerol synthesis; (c) translocation in the nucleus. Note that there are other targets of Hog1p such as Sic1p, Hsl1p, Nha1p, and Tok1p. (4) Nuclear Hog1PP induces a large transcriptional response. In particular, the gene GPD1 leading to glycerol synthesis is upregulated. Negative feedbacks (glycerol production, phosphorylation of Sho1p, etc.) allow inhibition of the pathway activity. (5) Increase of the internal glycerol leads to water influx and progressive cell size recovery while Hog1p is exported from the nucleus. (6) Pathway is off, and turgor pressure and cell size are restored. The cell is adapted to its new environment.