Osmotic stress signaling and osmoadaptation in yeasts

Abstract

The ability to adapt to altered availability of free water is a fundamental property of living cells. The principles underlying osmoadaptation are well conserved. The yeast Saccharomyces cerevisiae is an excellent model system with which to study the molecular biology and physiology of osmoadaptation. Upon a shift to high osmolarity, yeast cells rapidly stimulate a mitogen-activated protein (MAP) kinase cascade, the high-osmolarity glycerol (HOG) pathway, which orchestrates part of the transcriptional response. The dynamic operation of the HOG pathway has been well studied, and similar osmosensing pathways exist in other eukaryotes. Protein kinase A, which seems to mediate a response to diverse stress conditions, is also involved in the transcriptional response program. Expression changes after a shift to high osmolarity aim at adjusting metabolism and the production of cellular protectants. Accumulation of the osmolyte glycerol, which is also controlled by altering transmembrane glycerol transport, is of central importance. Upon a shift from high to low osmolarity, yeast cells stimulate a different MAP kinase cascade, the cell integrity pathway. The transcriptional program upon hypo-osmotic shock seems to aim at adjusting cell surface properties. Rapid export of glycerol is an important event in adaptation to low osmolarity. Osmoadaptation, adjustment of cell surface properties, and the control of cell morphogenesis, growth, and proliferation are highly coordinated processes. The Skn7p response regulator may be involved in coordinating these events. An integrated understanding of osmoadaptation requires not only knowledge of the function of many uncharacterized genes but also further insight into the time line of events, their interdependence, their dynamics, and their spatial organization as well as the importance of subtle effects.

FIG. 1.

Topology of Sho1p and Sln1p. Numbers indicate amino acid positions.

FIG. 2.

Nomenclature of proteins in MAP kinase pathways. Arrows only indicate the flow of information; pathway-specific protein complexes are common and are required for signal transmission.

FIG. 3.

Outline of the yeast MAP kinase pathways, illustrating similarities and difference in architecture. Gpa1p, Ste4p, and Ste18p form a heterotrimeric G-protein; Ras2p is one of two yeast Ras proteins. Other proteins are explained in the text.

FIG. 4.

Outline of the HOG pathway. Pbs2p functions both as a scaffold and as a MAPKKK; it is not known exactly with which components of the Sho1 branch it interacts.

FIG. 5.

Possible mechanism of feedback control of the HOG pathway, indicating protein phosphatases whose production is stimulated after osmotic shock. The production of glycerol leads to restoration of turgor and hence stops further activation of the pathway.

FIG. 6.

Model for the mechanisms with which the HOG pathway controls gene expression via Sko1p. Protein kinase A activity stimulates nuclear localization; some redistribution of Sko1/Acr1p to the cytosol is only observed under severe osmotic stress. Sko1/Acr1p may also have an activating function in addition to its demonstrated role as a repressor.

FIG. 7.

Domain organization of Hot1p and related yeast transcription factors. The putative DNA-binding domains are aligned, highlighting possible α-helices.

FIG. 8.

Outline of the cell integrity pathway. Two pathways acting in parallel, the calcineurin and the Ppz pathways, are indicated.

FIG. 9.

Model for the role of Skn7p. How oxidative stress or Rho1p activates Skn7p is not known. It is also not known where in the cell interaction between Skn7p and the Sln1p-Ypd1p system or the Rho1p GTP-binding protein occurs.

FIG. 10.

Model for the fission yeast Sty1 pathway. Mak2 and Mak3 seem to be sensors for oxidative stress and may form a phosphorelay system together with Mpr1 and Mcs4. Sensors for other stress conditions have not been identified yet.

FIG. 11.

Upper part of the glycolytic pathway and pathways for production of glycerol, trehalose, and glycogen, with all proteins and their isoforms indicated. Expression of the genes encoding the proteins that are underlined is stimulated after osmotic shock, and expression of those that are overlined is diminished.