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      Balancing of the mitotic exit network and cell wall integrity signaling governs the development and pathogenicity in Magnaporthe oryzae

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          Abstract

          The fungal cell wall plays an essential role in maintaining cell morphology, transmitting external signals, controlling cell growth, and even virulence. Relaxation and irreversible stretching of the cell wall are the prerequisites of cell division and development, but they also inevitably cause cell wall stress. Both Mitotic Exit Network (MEN) and Cell Wall Integrity (CWI) are signaling pathways that govern cell division and cell stress response, respectively, how these pathways cross talk to govern and coordinate cellular growth, development, and pathogenicity remains not fully understood. We have identified MoSep1, MoDbf2, and MoMob1 as the conserved components of MEN from the rice blast fungus Magnaporthe oryzae. We have found that blocking cell division results in abnormal CWI signaling. In addition, we discovered that MoSep1 targets MoMkk1, a conserved key MAP kinase of the CWI pathway, through protein phosphorylation that promotes CWI signaling. Moreover, we provided evidence demonstrating that MoSep1-dependent MoMkk1 phosphorylation is essential for balancing cell division with CWI that maintains the dynamic stability required for virulence of the blast fungus.

          Author summary

          The cell wall is a relatively rigid structure for supporting the cell shape and against extracellular stresses. However, it also maintains plasticity to cope with cell division, growth, and differentiation. In the rice blast pathogenic fungus Magnaporthe oryzae, such differentiation corresponds directly to its virulence. Thus, how to balance the “strong for shaping” with the “malleable for growth and virulence” poses as an important question of both basic- and applied science of significance. We here report that the protein kinase MoSep1 links the Mitotic Exit Network (MEN) to the Cell Wall Integrity (CWI) signaling through the phosphorylation of the CWI MAP kinase kinase MoMkk1. We found that the MoSep1-dependent phosphorylation of MoMkk1 relieves the cell wall stress caused by cell division and that the MEN-CWI-mediated balance of rigid and remodeling of the cell wall is important in the growth, development, and virulence of the blast fungus. Our study provides a new evidence on how the blast fungus adapts to self-generated stress for growth and virulence and it sheds new light on the crosstalk between MEN and CWI signaling.

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          Most cited references51

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          The Fungal Cell Wall: Structure, Biosynthesis, and Function.

          The molecular composition of the cell wall is critical for the biology and ecology of each fungal species. Fungal walls are composed of matrix components that are embedded and linked to scaffolds of fibrous load-bearing polysaccharides. Most of the major cell wall components of fungal pathogens are not represented in humans, other mammals, or plants, and therefore the immune systems of animals and plants have evolved to recognize many of the conserved elements of fungal walls. For similar reasons the enzymes that assemble fungal cell wall components are excellent targets for antifungal chemotherapies and fungicides. However, for fungal pathogens, the cell wall is often disguised since key signature molecules for immune recognition are sometimes masked by immunologically inert molecules. Cell wall damage leads to the activation of sophisticated fail-safe mechanisms that shore up and repair walls to avoid catastrophic breaching of the integrity of the surface. The frontiers of research on fungal cell walls are moving from a descriptive phase defining the underlying genes and component parts of fungal walls to more dynamic analyses of how the various components are assembled, cross-linked, and modified in response to environmental signals. This review therefore discusses recent advances in research investigating the composition, synthesis, and regulation of cell walls and how the cell wall is targeted by immune recognition systems and the design of antifungal diagnostics and therapeutics.
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            Plant cell wall-mediated immunity: cell wall changes trigger disease resistance responses.

            Plants have evolved a repertoire of monitoring systems to sense plant morphogenesis and to face environmental changes and threats caused by different attackers. These systems integrate different signals into overreaching triggering pathways which coordinate developmental and defence-associated responses. The plant cell wall, a dynamic and complex structure surrounding every plant cell, has emerged recently as an essential component of plant monitoring systems, thus expanding its function as a passive defensive barrier. Plants have a dedicated mechanism for maintaining cell wall integrity (CWI) which comprises a diverse set of plasma membrane-resident sensors and pattern recognition receptors (PRRs). The PRRs perceive plant-derived ligands, such as peptides or wall glycans, known as damage-associated molecular patterns (DAMPs). These DAMPs function as 'danger' alert signals activating DAMP-triggered immunity (DTI), which shares signalling components and responses with the immune pathways triggered by non-self microbe-associated molecular patterns that mediate disease resistance. Alteration of CWI by impairment of the expression or activity of proteins involved in cell wall biosynthesis and/or remodelling, as occurs in some plant cell wall mutants, or by wall damage due to colonization by pathogens/pests, activates specific defensive and growth responses. Our current understanding of how these alterations of CWI are perceived by the wall monitoring systems is scarce and few plant sensors/PRRs and DAMPs have been characterized. The identification of these CWI sensors and PRR-DAMP pairs will help us to understand the immune functions of the wall monitoring system, and might allow the breeding of crop varieties and the design of agricultural strategies that would enhance crop disease resistance.
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              Autophagic fungal cell death is necessary for infection by the rice blast fungus.

              Rice blast is caused by the fungus Magnaporthe grisea, which elaborates specialized infection cells called appressoria to penetrate the tough outer cuticle of the rice plant Oryza sativa. We found that the formation of an appressorium required, sequentially, the completion of mitosis, nuclear migration, and death of the conidium (fungal spore) from which the infection originated. Genetic intervention during mitosis prevented both appressorium development and conidium death. Impairment of autophagy, by the targeted mutation of the MgATG8 gene, arrested conidial cell death but rendered the fungus nonpathogenic. Thus, the initiation of rice blast requires autophagic cell death of the conidium.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: Methodology
                Role: InvestigationRole: Methodology
                Role: Data curation
                Role: Formal analysisRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Project administrationRole: Resources
                Role: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Pathog
                PLoS Pathog
                plos
                plospath
                PLoS Pathogens
                Public Library of Science (San Francisco, CA USA )
                1553-7366
                1553-7374
                7 January 2021
                January 2021
                : 17
                : 1
                : e1009080
                Affiliations
                [1 ] Department of Plant Pathology, College of Plant Protection, Nanjing Agricultural University, and Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing, China
                [2 ] The Key Laboratory of Plant Immunity, Nanjing Agricultural University, Nanjing, China
                [3 ] Departments of Microbiology, Immunology, and Parasitology, and Pediatrics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America
                Institute of Microbiology, CHINA
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-8253-4505
                Article
                PPATHOGENS-D-20-01324
                10.1371/journal.ppat.1009080
                7817018
                33411855
                7068b5a1-e961-4019-9967-99b3737e59b5
                © 2021 Feng et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 June 2020
                : 20 October 2020
                Page count
                Figures: 11, Tables: 0, Pages: 27
                Funding
                Funded by: NSFC-DFG
                Award ID: 31861133017
                Award Recipient :
                Funded by: Natural Science Foundation of China
                Award ID: Grant No.31671979
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100012226, Fundamental Research Funds for the Central Universities;
                Award ID: KYT201805
                Award Recipient :
                Funded by: Innovation Team Program for Jiangsu Universities
                Award ID: 2017
                Award Recipient :
                This study was supported by NSFC-DFG (Grant No.31861133017, URL: http://www.nsfc.gov.cn, grant recipient Z.Z) and Natural Science Foundation of China (Grant No.31671979, URL: http://www.nsfc.gov.cn, grant recipient X.Z), by Fundamental Research Funds for the Central Universities (Grant No.KYT201805, URL: http://kxyjy.njau.edu.cn, grant recipient Z.Z) and by Innovation Team Program for Jiangsu Universities (Grant No.2017, URL: http://www.ec.js.edu.cn, grant recipient Z.Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Proteins
                Post-Translational Modification
                Phosphorylation
                Biology and Life Sciences
                Cell Biology
                Cell Processes
                Cell Cycle and Cell Division
                Biology and Life Sciences
                Organisms
                Eukaryota
                Fungi
                Rice Blast Fungus
                Biology and Life Sciences
                Plant Science
                Plant Pathology
                Plant Pathogens
                Plant Fungal Pathogens
                Rice Blast Fungus
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Cell Walls
                Plant Cell Walls
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Plant Cells
                Plant Cell Walls
                Biology and Life Sciences
                Cell Biology
                Plant Cell Biology
                Plant Cells
                Plant Cell Walls
                Biology and Life Sciences
                Plant Science
                Plant Cell Biology
                Plant Cells
                Plant Cell Walls
                Biology and Life Sciences
                Organisms
                Eukaryota
                Plants
                Grasses
                Rice
                Research and Analysis Methods
                Animal Studies
                Experimental Organism Systems
                Plant and Algal Models
                Rice
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogenesis
                Biology and Life Sciences
                Mycology
                Fungal Structure
                Appressoria
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Cell Walls
                Custom metadata
                vor-update-to-uncorrected-proof
                2021-01-20
                All relevant data are within the paper and its Supporting information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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