Crosstalk between Saccharomyces cerevisiae SAPKs Hog1 and Mpk1 is mediated by glycerol accumulation

Laz, Ekaterina V.; Lee, Jongmin; Levin, David E.

doi:10.1016/j.funbio.2019.10.002

Cited by 11 publications

(3 citation statements)

References 31 publications

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“…This is the case with SDS [ 29 ] and zymolyase [ 42 ] treatments. Zymolyase, a mixture of cell-wall-digesting enzymes, promotes Slt2 activation partly because of Hog1-driven glycerol accumulation [ 66 ]. However, genome-wide expression studies found no induction of genes coding the prototypical glycerol-producing proteins GPD1 and GPD2 after treatment with antifungals targeting ergosterol biosynthesis, including clotrimazole [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Clotrimazole-Induced Oxidative Stress Triggers Novel Yeast Pkc1-Independent Cell Wall Integrity MAPK Pathway Circuitry

Sellers-Moya

Nuévalos

Molina

et al. 2021

JoF

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Azoles are one of the most widely used drugs to treat fungal infections. To further understand the fungal response to azoles, we analyzed the MAPK circuitry of the model yeast Saccharomyces cerevisiae that operates under treatment with these antifungals. Imidazoles, and particularly clotrimazole, trigger deeper changes in MAPK phosphorylation than triazoles, involving a reduction in signaling through the mating pathway and the activation of the MAPKs Hog1 and Slt2 from the High-Osmolarity Glycerol (HOG) and the Cell Wall Integrity (CWI) pathways, respectively. Clotrimazole treatment leads to actin aggregation, mitochondrial alteration, and oxidative stress, which is essential not only for the activation of both MAPKs, but also for the appearance of a low-mobility form of Slt2 caused by additional phosphorylation to that occurring at the conserved TEY activation motif. Clotrimazole-induced ROS production and Slt2 phosphorylation are linked to Tpk3-mediated PKA activity. Resistance to clotrimazole depends on HOG and CWI-pathway-mediated stress responses. However, Pkc1 and other proteins acting upstream in the pathway are not critical for the activation of the Slt2 MAPK module, suggesting a novel rewiring of signaling through the CWI pathway. We further show that the strong impact of azole treatment on MAPK signaling is conserved in other yeast species.

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Section: Discussionmentioning

confidence: 99%

Clotrimazole-Induced Oxidative Stress Triggers Novel Yeast Pkc1-Independent Cell Wall Integrity MAPK Pathway Circuitry

Sellers-Moya

Nuévalos

Molina

et al. 2021

JoF

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“…Glycerol seems to be a key mediator of the crosstalk between CWI and HOG pathways. Activation of Slt2 in response to zymolyase treatment is a consequence of Hog1-driven glycerol accumulation [117]. Moreover, heat-shock activates Hog1 via the CWI pathway, and the main role of the CWI in this process is to stimulate glycerol loss [118].…”

Section: Cell Wall-stress Conditionsmentioning

confidence: 99%

Control of Gene Expression via the Yeast CWI Pathway

Sanz

García

Pavón-Vergés

et al. 2022

IJMS

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Living cells exposed to stressful environmental situations can elicit cellular responses that guarantee maximal cell survival. Most of these responses are mediated by mitogen-activated protein kinase (MAPK) cascades, which are highly conserved from yeast to humans. Cell wall damage conditions in the yeast Saccharomyces cerevisiae elicit rescue mechanisms mainly associated with reprogramming specific transcriptional responses via the cell wall integrity (CWI) pathway. Regulation of gene expression by this pathway is coordinated by the MAPK Slt2/Mpk1, mainly via Rlm1 and, to a lesser extent, through SBF (Swi4/Swi6) transcription factors. In this review, we summarize the molecular mechanisms controlling gene expression upon cell wall stress and the role of chromatin structure in these processes. Some of these mechanisms are also discussed in the context of other stresses governed by different yeast MAPK pathways. Slt2 regulates both transcriptional initiation and elongation by interacting with chromatin at the promoter and coding regions of CWI-responsive genes but using different mechanisms for Rlm1- and SBF-dependent genes. Since MAPK pathways are very well conserved in eukaryotic cells and are essential for controlling cellular physiology, improving our knowledge regarding how they regulate gene expression could impact the future identification of novel targets for therapeutic intervention.

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“…Fps1 is under the control of the CWI pathway (Ahmadpour et al, 2016, Laz et al, 2020). In yeast, when the cell wall is damaged, water flows into the cell driven by the osmotic pressure difference between the inside and outside of the cell.…”

Section: Introductionmentioning

confidence: 99%

The CWI pathway is activated through high hydrostatic pressure, enhancing glycerol efflux via the aquaglyceroporin Fps1 inSaccharomyces cerevisiae

Mochizuki

Tanigawa

Shindo

et al. 2022

Preprint

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The fungal cell wall is the first barrier against diverse external stresses, such as high hydrostatic pressure. This study explores the roles of osmoregulation and the cell wall integrity (CWI) pathway in response to the high pressure in the yeast Saccharomyces cerevisiae. We demonstrate the roles of the transmembrane mechanosensor Wsc1 and aquaglyceroporin Fps1 in an underlying protective mechanism to avoid cellular rupture under high pressure. The promotion of water influx into cells at 25 MPa, as evident by an increase in cell volume and a loss of the plasma membrane eisosome structure, promotes the activation of Wsc1, an activator of the CWI pathway. The downstream mitogen-activated protein kinase Slt2 was hyperphosphorylated at 25 MPa. Glycerol efflux increases via Fps1 phosphorylation, which is initiated by downstream components of the CWI pathway, and contributes to the reduction in intracellular osmolarity under high pressure. Herein, the elucidation of a cellular pathway that is used as a protective mechanism against high pressure could potentially be translated to mammalian cells and could help to understand cellular mechanosensation and adaptation.

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Crosstalk between Saccharomyces cerevisiae SAPKs Hog1 and Mpk1 is mediated by glycerol accumulation

Cited by 11 publications

References 31 publications

Clotrimazole-Induced Oxidative Stress Triggers Novel Yeast Pkc1-Independent Cell Wall Integrity MAPK Pathway Circuitry

Clotrimazole-Induced Oxidative Stress Triggers Novel Yeast Pkc1-Independent Cell Wall Integrity MAPK Pathway Circuitry

Control of Gene Expression via the Yeast CWI Pathway

The CWI pathway is activated through high hydrostatic pressure, enhancing glycerol efflux via the aquaglyceroporin Fps1 inSaccharomyces cerevisiae

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