Regulation of the Osmoregulatory HOG MAPK Cascade in Yeast

Saito, Haruo; Tatebayashi, Kazuo

doi:10.1093/jb/mvh135

Cited by 215 publications

(194 citation statements)

References 51 publications

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“…Once pathway activation was turned off, phosphatases caused inactivation of Hog1 and hence pathway downregulation. Although the model contains a moderate upregulation of phosphatase activity in accordance with experimental reports 24 , a very similar pathway downregulation was observed when phosphatase activity was kept constant in simulations (data not shown). We performed a sensitivity analysis to test the influence of the parameter choice on the quality of the fit ( Supplementary Fig.…”

Section: Time Course Experimentssupporting

confidence: 85%

Integrative model of the response of yeast to osmotic shock

et al. 2005

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Integration of experimental studies with mathematical modeling allows insight into systems properties, prediction of perturbation effects and generation of hypotheses for further research. We present a comprehensive mathematical description of the cellular response of yeast to hyperosmotic shock. The model integrates a biochemical reaction network comprising receptor stimulation, mitogen-activated protein kinase cascade dynamics, activation of gene expression and adaptation of cellular metabolism with a thermodynamic description of volume regulation and osmotic pressure. Simulations agree well with experimental results obtained under different stress conditions or with specific mutants. The model is predictive since it suggests previously unrecognized features of the system with respect to osmolyte accumulation and feedback control, as confirmed with experiments. The mathematical description presented is a valuable tool for future studies on osmoregulation in yeast and-with appropriate modifications-other organisms. It also serves as a starting point for a comprehensive description of cellular signaling.Osmoregulation encompasses active processes with which cells monitor and adjust osmotic pressure and control shape, turgor and relative water content. Even individual cells in multicellular organisms respond to osmotic changes, and strategies of cellular adaptation are conserved from bacteria to human 1 . The yeast Saccharomyces cerevisiae is a suitable model system to study osmoregulation and a substantial amount of information is available on osmotic shockinduced signal transduction, control of gene expression and accumulation of osmolytes 2 .Osmoregulation is a homeostatic process, though commonly studied as a response to osmotic shock. Central to yeast osmotic adaptation is the high osmolarity glycerol (HOG) signaling system 2,3 (Fig. 1). S. cerevisiae monitors osmotic changes through the plasma membrane-localized sensor histidine kinase Sln1. Under ambient conditions, Sln1 is active and inhibits signaling. Upon loss of turgor pressure, Sln1 is inactivated 4 resulting in activation of a mitogen-activated protein (MAP) kinase cascade and phosphorylation of the MAP kinase Hog1. Active Hog1 accumulates in the nucleus where it affects gene expression. Two HOG target genes encode enzymes in glycerol production. Hence, activation of Hog1 stimulates the production of glycerol, which serves as an osmolyte to increase intracellular osmotic pressure. Glycerol accumulation is also controlled by rapid closing of the aquaglyceroporin Fps1, which is an osmolarity-regulated glycerol channel. Hog1 activation and Hog1-dependent transcriptional stimulation are transient processes, indicating rigorous feedback control. Several protein phosphatases are known as negative regulators of the pathway. Although the overall organization of the systems is well characterized, open questions concern the mechanisms underlying activation and deactivation of the system, feedback control and the causal relationship between different events in...

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Section: Time Course Experimentssupporting

confidence: 85%

Integrative model of the response of yeast to osmotic shock

et al. 2005

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“…Abolishment of hyperosmosis-induced growth arrest of SOD1Δ by AsA The delay of SOD1Δ cell growth in hyperand accumulation of the compatible solute glycerol, which is partly controlled by the high osmolarity glycerol (HOG) signaling system (Saito and Tatebayashi, 2004;Hohmann et al, 2007). Upon osmotic shock, a number of genes encoding enzymes implicated in oxidative damage repair are also induced under the control of the HOG pathway and the general stress response (Garay-Arroyo et al, 2003;Hohmann et al, 2007).…”

Section: Sod1 Sod2mentioning

confidence: 99%

A Simple Growth Test of a Saccharomyces cerevisiae Cu, Zn-Superoxide Dismutase-Deficient Mutant in Hypertonic Medium for Biological Evaluation of Antioxidants

Tamura¹,

Wada²,

Hase³

et al. 2010

FSTR

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Osmotic stress hampers the growth of Saccharomyces cerevisiae, and this effect is mediated by oxidative stress. A simple test for the biological evaluation of antioxidants was developed on the basis of recovery of growth delay of Cu, Zn-superoxide dismutase-lacking yeast (SOD1Δ) under hyperosmosis. The SOD1Δ strain suffered from growth inhibition in a medium containing 1.7 M sorbitol. Protein oxidation in SOD1Δ cells was greatly increased by exposure to a hypertonic medium, indicating the accumulation of reactive oxygen species followed by oxidation of cellular materials. The hyperosmosis-induced growth arrest of SOD1Δ was abolished by the addition of L-ascorbic acid to the medium; the antioxidant effect depended on the concentration, ranging from 1 to 10 mM. Cysteine, N-acetyl-cysteine, and glutathione were also able to restore the growth of SOD1Δ cells. High concentrations of these thiol compounds proved less effective, probably due to adverse effects of an excess of these antioxidants. No growth restoration was seen for typical polyphenol antioxidants, including curcumin, quercetin and catechin.

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“…The mitogen-activated protein (MAP) kinase pathways have evolved as highly efficient, multipurpose signal transduction systems. S. cerevisiae uses multiple MAP kinase pathways, each one for a distinct signaling system, including the mating process, the filamentation process, cell wall integrity, ascospore formation, and osmoregulation (Levin and Errede, 1995;Gustin et al, 1998;Saito and Tatebayashi, 2004;Chen and Thorner, 2007). Several of these pathways share a limited number of components, but all are presumed to use different receptors to elicit very different responses.…”

Section: Introductionmentioning

confidence: 99%

The Same Receptor, G Protein, and Mitogen-activated Protein Kinase Pathway Activate Different Downstream Regulators in the Alternative White and Opaque Pheromone Responses ofCandida albicans

Song

Sahni

Daniels

et al. 2008

MBoC

251

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Candida albicans must undergo a switch from white to opaque to mate. Opaque cells then release mating type-specific pheromones that induce mating responses in opaque cells. Uniquely in C. albicans, the same pheromones induce mating-incompetent white cells to become cohesive, form an adhesive basal layer of cells on a surface, and then generate a thicker biofilm that, in vitro, facilitates mating between minority opaque cells. Through mutant analysis, it is demonstrated that the pathways regulating the white and opaque cell responses to the same pheromone share the same upstream components, including receptors, heterotrimeric G protein, and mitogen-activated protein kinase cascade, but they use different downstream transcription factors that regulate the expression of genes specific to the alternative responses. This configuration, although common in higher, multicellular systems, is not common in fungi, and it has not been reported in Saccharomyces cerevisiae. The implications in the evolution of multicellularity in higher eukaryotes are discussed. INTRODUCTIONBoth single cell organisms and the individual cells of multicellular organisms must respond to a variety of environmental signals (Dorsky et al., 2000;Balázsi and Oltvai, 2005). In addition, in higher eukaryotes different cell types frequently respond to the same signal in unique ways (Rincón and Pedraza-Alva, 2003;Bacci et al., 2005;Dailey et al., 2005). In most cases, different signals interact with unique surface receptors that activate different signal transduction pathways, as has been demonstrated in Saccharomyces cerevisiae (Leberer et al., 1997;Gustin et al., 1998;Madhani and Fink, 1998;Elion, 2000). The mitogen-activated protein (MAP) kinase pathways have evolved as highly efficient, multipurpose signal transduction systems. S. cerevisiae uses multiple MAP kinase pathways, each one for a distinct signaling system, including the mating process, the filamentation process, cell wall integrity, ascospore formation, and osmoregulation (Levin and Errede, 1995;Gustin et al., 1998;Saito and Tatebayashi, 2004;Chen and Thorner, 2007). Several of these pathways share a limited number of components, but all are presumed to use different receptors to elicit very different responses. In the mating process of S. cerevisiae, a cells release a-factor that interacts with the a-receptor on ␣ cells, and ␣ cells release ␣-factor that interacts with the ␣-receptor on a cells. These alternative signals are then transduced through the same heterotrimeric G protein to activate the same MAP kinase pathway, which in turn activates the same downstream regulators that elicit similar mating responses, including G1 arrest, polarization, and shmooing (Sprague et al., 1983;Bender and Sprague, 1986;Leberer et al., 1997). Other fungi, including Magnaporthe grisea (Dixon et al., 1999;Zhao et al., 2005b) Neurospora crassa (Li et al., 2005), and Cryptococcus neoformans (Davidson et al., 2003;Kraus et al., 2003;Bahn et al., 2005) also use MAP kinase pathways for a variety of responses...

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Regulation of the Osmoregulatory HOG MAPK Cascade in Yeast

Cited by 215 publications

References 51 publications

Integrative model of the response of yeast to osmotic shock

Integrative model of the response of yeast to osmotic shock

A Simple Growth Test of a Saccharomyces cerevisiae Cu, Zn-Superoxide Dismutase-Deficient Mutant in Hypertonic Medium for Biological Evaluation of Antioxidants

The Same Receptor, G Protein, and Mitogen-activated Protein Kinase Pathway Activate Different Downstream Regulators in the Alternative White and Opaque Pheromone Responses ofCandida albicans

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