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

2021 ◽  
Vol 7 (8) ◽  
pp. 647
Author(s):  
Ángela Sellers-Moya ◽  
Marcos Nuévalos ◽  
María Molina ◽  
Humberto Martín
Keyword(s):  
Oxidative Stress ◽  
Cell Wall ◽  
Stress Responses ◽  
Fungal Infections ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Cell Wall Integrity ◽  
Strong Impact ◽  
Yeast Saccharomyces Cerevisiae ◽  
Activation Motif

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.

scholarly journals Yeast Nap1-Binding Protein Nbp2p Is Required for Mitotic Growth at High Temperatures and for Cell Wall Integrity

Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 517-529
Author(s):  
Kentaro Ohkuni ◽  
Asuko Okuda ◽  
Akihiko Kikuchi
Keyword(s):  
Cell Death ◽  
Cell Wall ◽  
High Temperature ◽  
High Temperatures ◽  
Hybrid System ◽  
Mapk Pathway ◽  
Binding Protein ◽  
Cell Wall Integrity ◽  
Calcofluor White ◽  
Two Hybrid

AbstractNbp2p is a Nap1-binding protein in Saccharomyces cerevisiae identified by its interaction with Nap1 by a two-hybrid system. NBP2 encodes a novel protein consisting of 236 amino acids with a Src homology 3 (SH3) domain. We showed that NBP2 functions to promote mitotic cell growth at high temperatures and cell wall integrity. Loss of Nbp2 results in cell death at high temperatures and in sensitivity to calcofluor white. Cell death at high temperature is thought not to be due to a weakened cell wall. Additionally, we have isolated several type-2C serine threonine protein phosphatases (PTCs) as multicopy suppressors and MAP kinase-kinase (MAPKK), related to the yeast PKC MAPK pathway, as deletion suppressors of the nbp2Δ mutant. Screening for deletion suppressors is a new genetic approach to identify and characterize additional proteins in the Nbp2-dependent pathway. Genetic analyses suggested that Ptc1, which interacts with Nbp2 by the two-hybrid system, acts downstream of Nbp2 and that cells lacking the function of Nbp2 prefer to lose Mkk1, but the PKC MAPK pathway itself is indispensable when Nbp2 is deleted at high temperature.

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

FEBS Letters ◽  
2013 ◽  
Vol 587 (22) ◽  
pp. 3675-3680 ◽  
Author(s):  
José M. Rodríguez-Peña ◽  
Sonia Díez-Muñiz ◽  
Clara Bermejo ◽  
César Nombela ◽  
Javier Arroyo
Keyword(s):  
Cell Wall ◽  
Yeast Cell ◽  
Mapk Pathway ◽  
Cell Wall Integrity ◽  
Yeast Cell Wall

scholarly journals The plant cell wall integrity maintenance and immune signaling systems cooperate to control stress responses inArabidopsis thaliana

2018 ◽  
Vol 11 (536) ◽  
pp. eaao3070 ◽  
Author(s):  
Timo Engelsdorf ◽  
Nora Gigli-Bisceglia ◽  
Manikandan Veerabagu ◽  
Joseph F. McKenna ◽  
Lauri Vaahtera ◽  
...  
Keyword(s):  
Cell Wall ◽  
Plant Cell ◽  
Stress Responses ◽  
Plant Cell Wall ◽  
Cell Wall Integrity ◽  
Immune Signaling ◽  
Signaling Systems

scholarly journals Quercetin Protects Saccharomyces cerevisiae against Oxidative Stress by Inducing Trehalose Biosynthesis and the Cell Wall Integrity Pathway

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e45494 ◽  
Author(s):  
Rita Vilaça ◽  
Vanda Mendes ◽  
Marta Vaz Mendes ◽  
Laura Carreto ◽  
Maria Amélia Amorim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Cell Wall Integrity ◽  
Cell Wall Integrity Pathway ◽  
Trehalose Biosynthesis

Amiodarone induces stress responses and calcium flux mediated by the cell wall in Saccharomyces cerevisiae

2009 ◽  
Vol 55 (3) ◽  
pp. 288-303 ◽  
Author(s):  
William E. Courchesne ◽  
Meral Tunc ◽  
Sha Liao
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Stress Responses ◽  
Inhibitory Effect ◽  
Calcium Flux ◽  
Yeast Saccharomyces Cerevisiae ◽  
Proteomic Approach ◽  
Amiodarone Treatment ◽  
Kinetics Of

We used a proteomic approach to study effects of amiodarone on cells of the yeast Saccharomyces cerevisiae. Amiodarone has been shown to have antifungal activity in vitro and causes a massive increase in cytoplasmic calcium levels ([Ca2+]cyt). Proteomic analysis of cells exposed to amiodarone show that this drug elicits stress responses and points to involvement of proteins associated with the cell wall. We tested several of those proteins for involvement in the Ca2+ flux. In particular, the amiodarone-induced Ca2+ flux was decreased in bgl2Δ cells, which have altered levels of β-glucan and chitin. The involvement of the cell wall in the Ca2+ flux induced by amiodarone treatment was tested by addition of yeast cell-wall components. While mannan inhibited the rise in [Ca2+]cyt, β-glucan potentiated the Ca2+ flux by 4.5-fold, providing evidence that the cell wall is directly involved in controlling this Ca2+ flux. This conclusion is corroborated by the inhibition of the Ca2+ flux by calcofluor, which is known to bind to cell-wall chitin and inhibit cell growth. Zymolyase treatment altered the kinetics of amiodarone-induced calcium flux and uncoupled the inhibitory effect of calcofluor. These effects demonstrate that the cell-wall β-glucan regulates calcium flux elicited by amiodarone.

Overview of the Interplay Between Cell Wall Integrity Signaling Pathways and Membrane Lipid Biosynthesis in Fungi: Perspectives forAspergillus fumigatus

2020 ◽  
Vol 21 (3) ◽  
pp. 265-283 ◽  
Author(s):  
João Henrique T.M. Fabri ◽  
Marina C. Rocha ◽  
Iran Malavazi
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Signaling Pathways ◽  
Fungal Infections ◽  
Invasive Pulmonary Aspergillosis ◽  
Pathogenic Fungi ◽  
Cell Wall Integrity ◽  
Immune Recognition ◽  
Fungal Cell ◽  
Low Efficiency

:The cell wall (CW) and plasma membrane are fundamental structures that define cell shape and support different cellular functions. In pathogenic fungi, such as Aspegillus fumigatus, they not only play structural roles but are also important for virulence and immune recognition. Both the CW and the plasma membrane remain as attractive drug targets to treat fungal infections, such as the Invasive Pulmonary Aspergillosis (IPA), a disease associated with high morbimortality in immunocompromised individuals. The low efficiency of echinocandins that target the fungal CW biosynthesis, the occurrence of environmental isolates resistant to azoles such as voriconazole and the known drawbacks associated with amphotericin toxicity foster the urgent need for fungal-specific drugable targets and/or more efficient combinatorial therapeutic strategies. Reverse genetic approaches in fungi unveil that perturbations of the CW also render cells with increased susceptibility to membrane disrupting agents and vice-versa. However, how the fungal cells simultaneously cope with perturbation in CW polysaccharides and cell membrane proteins to allow morphogenesis is scarcely known. Here, we focus on current information on how the main signaling pathways that maintain fungal cell wall integrity, such as the Cell Wall Integrity and the High Osmolarity Glycerol pathways, in different species often cross-talk to regulate the synthesis of molecules that comprise the plasma membrane, especially sphingolipids, ergosterol and phospholipids to promote functioning of both structures concomitantly and thus, cell viability. We propose that the conclusions drawn from other organisms are the foundations to point out experimental lines that can be endeavored in A. fumigatus.

scholarly journals The MAPKKK CgMck1 Is Required for Cell Wall Integrity, Appressorium Development, and Pathogenicity in Colletotrichum gloeosporioides

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 543 ◽  
Author(s):  
Yu-Lan Fang ◽  
Li-Ming Xia ◽  
Ping Wang ◽  
Li-Hua Zhu ◽  
Jian-Ren Ye ◽  
...  
Keyword(s):  
Cell Wall ◽  
Vegetative Growth ◽  
Colletotrichum Gloeosporioides ◽  
Mapk Signaling ◽  
Cell Wall Integrity ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signals ◽  
Mapk Cascades ◽  
Body Development ◽  
Mitogen Activated Protein

Mitogen-activated protein kinase (MAPK) signaling pathway plays key roles in sensing extracellular signals and transmitting them from the cell membrane to the nucleus in response to various environmental stimuli. A MAPKKK protein CgMck1 in Colletotrichum gloeosporioides was characterized. Phenotypic analyses of the ∆Cgmck1 mutant showed that the CgMck1 was required for vegetative growth, fruiting body development, and sporulation. Additionally, the CgMCK1 deletion mutant showed significant defects in cell wall integrity, and responses to osmotic stresses. The mutant abolished the ability to develop appressorium, and lost pathogenicity to host plants. The ∆Cgmck1 mutant also exhibited a higher sensitivity to antifungal bacterium agent Bacillus velezensis. The deletion mutants of downstream MAPK cascades components CgMkk1 and CgMps1 showed similar defects to the ∆Cgmck1 mutant. In conclusion, CgMck1 is involved in the regulation of vegetative growth, asexual development, cell wall integrity, stresses resistance, and infection morphogenesis in C. gloeosporioides.

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