Stress resistance and signal fidelity independent of nuclear MAPK function

Abstract

Elevated external solute stimulates a conserved MAPK cascade that elicits responses that maintain osmotic balance. The yeast highosmolarity glycerol (HOG) pathway activates Hog1 MAPK (mammalian ortholog p38␣/SAPK␣), which enters the nucleus and induces expression of >50 genes, implying that transcriptional upregulation is necessary to cope with hyperosmotic stress. Contrary to this expectation, we show here that cells lacking the karyopherin required for Hog1 nuclear import or in which Hog1 is anchored at the plasma membrane (or both) can withstand longterm hyperosmotic challenge by ionic and nonionic solutes without exhibiting the normal change in transcriptional program (comparable with hog1⌬ cells), as judged by mRNA hybridization and microarray analysis. For such cells to survive hyperosmotic stress, systematic genetic analysis ruled out the need for any Hog1-dependent transcription factor, the Hog1-activated MAPKAP kinases, or ion, glycerol, and water channels. By contrast, enzymes needed for glycerol production were essential for viability. Thus, control of intracellular glycerol formation by Hog1 is critical for maintenance of osmotic balance but not transcriptional induction of any gene.hyperosmotic stress ͉ mutants ͉ protein kinase ͉ signal transduction ͉ yeast

Competition ofCandida glabrataagainstLactobacillusis Hog1 dependent

“…CgHog1 becomes phosphorylated but seems not to translocate into the nucleus. In fact, ScHog1 and CaHog1 translocation to the nucleus is not required for the activation of downstream events (Westfall et al, 2008, Lee et al, 2017, Day et al, 2017). Even though CgHog1 upon H 2 O 2 challenge does not enrich in the nucleus, this does not exclude cycling between nucleus and cytosol.…”

Analysis of osmoadaptation system in budding yeast suggests that regulated degradation of glycerol synthesis enzyme is key to near-perfect adaptation

“…Further, the study has suggested that such regulation diverts metabolic flux from biomass to intermediates of glycerol and therefore ensures stable glycerol flux (Petelenz-Kurdziel et al 2013). Also Westfall et al (2008) have shown that Hog1PP dependence is critical for the glycerol synthesis during hyper osmotic stress. Therefore, in the current model, we assumed that the glycerol synthesis is mainly regulated by the enzyme E and Hog1PP.…”

“…The other two mutants that did not include the enzyme dependence on glycerol synthesis indicate that a necessary condition for adaptation is the synthesis of glycerol through enzyme synthesised by transcriptional Hog1PP. It should be noted that near-perfect adaptation may not be necessary for the survival of cell, hence non-transcriptional effect of Hog1PP may be sufficient for the cell to survive (Westfall et al 2008). The utility of Hog1PP in glycerol synthesis in addition to the enzyme dependence (i.e.…”

Using Noise for Model-Testing

“…It is also a popular pathway in yeast for benchmark studies. The kinase activity of Hog1 in the cytoplasm leads to the production of glycerol (Westfall et al, 2008), which allows the cells to equilibrate interior and exterior osmotic pressures (Fig. 2).…”