MAP Kinase-Mediated Stress Relief that Precedes and Regulates the Timing of Transcriptional Induction

Abstract

In yeast, hyperosmotic stress causes an immediate dissociation of most proteins from chromatin, presumably because cells are unprepared for, and initially unresponsive to, increased ion concentrations in the nucleus. Osmotic stress activates Hog1 MAP kinase, which phosphorylates at least two proteins located at the plasma membrane, the Nha1 Na+/H+ antiporter and the Tok1 potassium channel. Hog1 phosphorylation stimulates Nha1 activity, and this is crucial for the rapid reassociation of proteins with their target sites in chromatin. This initial response to hyperosmolarity precedes and temporally regulates the activation of stress-response genes that depends on Hog1 phosphorylation of transcription factors in the nucleus. Thus, a single MAP kinase coordinates temporally, spatially, and mechanistically distinct responses to stress, thereby providing very rapid stress relief that facilitates subsequent changes in gene expression that permit long-term adaptation to harsh environmental conditions.

Genomic adaptations of the halophilic Dead Sea filamentous fungus Eurotium rubrum

“…Hardly any of the known short-term hypersalinity responses, for example, the HOG pathway 28 , cell wall integrity 29 , and ion homoeostasis via the Ca 2 þ /calmodulin signalling pathway 30 were reflected by gene expression changes in E. rubrum under long-term hypo-and hypersaline stress. However, the glycerol-3-phosphate dehydrogenase, a key enzyme in the production of the compatible osmolyte glycerol 10 , is upregulated as in other halophilic fungi 31 .…”

Novel stress responses facilitate Saccharomyces cerevisiae growth in the presence of the monocarboxylate preservatives

“…[20] This is highly analogous to the manner by which Hog1p acts to alleviate salt stress in S. cerevisiae, a situation where this same Hog1p MAP kinase -but now a Hog1p fraction bound in unstressed cells to cytosolic domains of the Nha1p and Tok1p plasma membrane ion transporters -generates instant stress relief whenever there is an activation of HOG pathway signalling by salt addtion (Hog1p stimulation of the Nha1p Na + /H + antiporter activity following salt stress is practically instant, preceding any Hog1p-dependent changes in gene transcription). [27] With an acetic acid addition to low-pH, glucoserepressed cultures of S. cerevisiae, acid uptake is enhanced and cells are rendered acetic acidsensitive, should Fps1p not become endocytosed but remain in the cell membrane (as occurs in the hog1 mutant, with the expression of nonphosphorylatable mutant forms of Fps1p, or in mutants with endocytosis defects). [20] Therefore, Hog1p-directed destabilization of Fps1p, eliminating the route for acetic acid entry to the cell, generates a resistance to levels of acetic acid that would otherwise prove toxic.…”

“…[19] Futhermore, osmoadaptation involves an altered expression of a large number of genes, ∼10% of the total yeast genome. [21] To a large extent this occurs through the Hog1p activated by osmostress being translocated to the nucleus where, by phosphorylation of a number of transcriptional activities, [27] it triggers roughly half of all of the gene induction or repression events in osmostressed cells. [21] In contrast, the same transcriptional regulators do not exert strong effects over acetic acid resistance (our unpublished observations).…”

Growth rate controls mRNA turnover in steady and non-steady states

“…It has been seen that initial osmotic shock provokes shrinkage of cells and suddenly varies macromolecule concentrations and washes out RNA pol II and transcription factors from chromatin. 35 This specific drop in transcription rates at the beginning of the stress response, when iGR is still high (Fig. S1), probably explains the distinctive profile of osmotic stress responses.…”