The sequential activation of the yeast HOG and SLT2 pathways is required for cell survival to cell wall stress

Bermejo, Clara; Rodríguez, Estefanía; García, Raúl; Rodríguez-Peña, Jose M.; Rodríguez de la Concepción, María L.; Rivas, Carmen; Arias, Patricia; Nombela, César; Posas, Francesc; Arroyo, Javier

doi:10.1091/mbc.e07-08-0742

Cited by 204Fungal and yeast genetics researchBacterial Genetics and BiotechnologyProtein Kinase Regulation and GTPase Signaling

The sequential activation of the yeast HOG and SLT2 pathways is required for cell survival to cell wall stress

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Bermejo, Clara, Rodríguez, Estefanía, García, Raúl, Rodríguez-Peña, Jose M., Rodríguez de la Concepción, María L., Rivas, Carmen, Arias, Patricia, Nombela, César +2 more·2008·Molecular Biology of the Cell

DOI 10.1091/mbc.e07-08-0742PMC PMC2262984

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Abstract

Yeast mitogen-activated protein kinase (MAPK) signaling pathways transduce external stimuli into cellular responses very precisely. The MAPKs Slt2/Mpk1 and Hog1 regulate transcriptional responses of adaptation to cell wall and osmotic stresses, respectively. Unexpectedly, we observe that the activation of a cell wall integrity (CWI) response to the cell wall damage caused by zymolyase (β-1,3 glucanase) requires both the HOG and SLT2 pathways. Zymolyase activates both MAPKs and Slt2 activation depends on the Sho1 branch of the HOG pathway under these conditions. Moreover, adaptation to zymolyase requires essential components of the CWI pathway, namely the redundant MAPKKs Mkk1/Mkk2, the MAPKKK Bck1, and Pkc1, but it does not require upstream elements, including the sensors and the guanine nucleotide exchange factors of this pathway. In addition, the transcriptional activation of genes involved in adaptation to cell wall stress, like CRH1, depends on the transcriptional factor Rlm1 regulated by Slt2, but not on the transcription factors regulated by Hog1. Consistent with these findings, both MAPK pathways are essential for cell survival under these circumstances because mutant strains deficient in different components of both pathways are hypersensitive to zymolyase. Thus, a sequential activation of two MAPK pathways is required for cellular adaptation to cell wall damage.

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Protein kinase C, high osmolarity glycerol response, and Ca2+-calcineurin pathways have been implicated in the response to cell wall damage and chitin synthesis.
“Protein kinase C (PKC), high osmolarity glycerol response (HOG), and Ca+2-calcineurin pathways have been implicated in the response to cell wall damage and chitin synthesis (Figure 1B; Lagorce et al., 2003; Bermejo et al., 2008; Walker et al., 2008; Fortwendel et al., 2009).”
From Fungal Cell Wall: Emerging Antifungals and Drug Resistance. (2019) · cites this paper as Bermejo et al., 2008

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Self-citation
Activation of the yeast cell wall integrity MAPK pathway by zymolyase depends on protease and glucanase activities and requires the mucin‐like protein Hkr1 but not Msb2
Rodríguez-Peña, J. M., Díez-Muñiz, S., Bermejo, C., Nombela, C., & Arroyo, J. (2013) · FEBS Letters · doi:10.1016/j.febslet.2013.09.030 · Cited by 40 · see citing works
Self-citation
Cell wall perturbation in yeast results in dual phosphorylation of the Slt2/Mpk1 MAP kinase and in an Slt2-mediated increase in FKS2–lacZ expression, glucanase resistance and thermotolerance
de Nobel, H., Ruiz, C., Martı́n, H., Morris, W. L., Brul, S., Molina, M., & Klis, F. M. (2000) · Microbiology · doi:10.1099/00221287-146-9-2121 · Cited by 269 · see citing works
The high‐osmolarity glycerol (HOG) and cell wall integrity (CWI) signalling pathways interplay: a yeast dialogue between MAPK routes
Rodríguez-Peña, J. M., García, R., Nombela, C., & Arroyo, J. (2010) · Yeast · doi:10.1002/yea.1792 · Cited by 182 · see citing works
Self-citation
Genome-wide survey of yeast mutations leading to activation of the yeast cell integrity MAPK pathway: Novel insights into diverse MAPK outcomes
Arias, P., Díez-Muñiz, S., García, R., Nombela, C., Rodríguez-Peña, J. M., & Arroyo, J. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-390 · Cited by 52 · see citing works
Self-citation

Authors: Bermejo, C., Rodríguez, E., García, R., Rodríguez-Peña, J. M., Rodríguez de la Concepción, M. L., Rivas, C., Arias, P., Nombela, C., Posas, F., & Arroyo, J.
Affiliations: Universidad Complutense de Madrid (ES)
*Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain; and
Cell Signalling Unit, Department de Ciènces Experimentals I de la Salut, Universitat Pompeu Fabra (UPF), Parc de Recerca Biomèdica de Barcelona (PRBB), E-08003 Barcelona, Spain
Universitat Pompeu Fabra (ES)
ORCID: Bermejo, Clara
Rodríguez, Estefanía
García, Raúl
Rivas, Carmen
Nombela, César
Posas, Francesc
Arroyo, Javier
Venue: Molecular Biology of the Cell
Publisher: American Society for Cell Biology (ASCB)
Published: 2008-03
Volume: 19
Issue: 3
Pages: 1113-1124
ISSN: 1059-1524 (ISSN-L)
1939-4586
DOI: 10.1091/mbc.e07-08-0742
PMC: PMC2262984
OpenAlex: W2103491947
Cited by: 204
References: 60
Citations by year: 2026: 11 · 2025: 4 · 2024: 8 · 2023: 6 · 2022: 9 · 2021: 7 · 2020: 8 · 2019: 9 · 2018: 9 · 2017: 6 · 2016: 16 · 2015: 18 · 2014: 17 · 2013: 7 · 2012: 15
FWCI: 7.41
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Molecular Biology of the Cell (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Johns Hopkins University
Ministerio de Economía y Competitividad
Universitat de Lleida
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords: HOG pathway, cell wall integrity, MAPK signaling, zymolyase, β-1,3-glucanase, cell wall stress, osmotic stress, Sho1, PKC1, Rlm1, Saccharomyces cerevisiae, stress adaptation, cell survival
MeSH terms: Adaptation, Physiological, Cell Wall, Enzyme Activation, Hydrolases, Mutation, Phosphorylation, Saccharomyces cerevisiae, Transcriptional Activation, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Saccharomyces cerevisiae Proteins, Microbial Viability

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The sequential activation of the yeast HOG and SLT2 pathways is required for cell survival to cell wall stress

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