{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:27:00Z","timestamp":1787563620850,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013620","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000}}],"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["2381\/15, 420\/17 and 927\/22"],"award-info":[{"award-number":["2381\/15, 420\/17 and 927\/22"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Russell Berrie Nanotechnology Institute, Technion","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Fungal pathogens employ conserved signaling pathways to survive in the host. The stress-activated MAP kinase Hog1 of the maize pathogen\n                    <jats:italic>Cochliobolus heterostrophus<\/jats:italic>\n                    undergoes dephosphorylation upon exposure to ferulic acid, a phenolic compound abundant in the host plant. Unlike its nuclear localization during osmotic stress, Hog1 forms cytoplasmic foci in response to FA, indicating its sequestering to a compartment or condensate. FA prevents several characteristic responses of the Hog1 pathway to osmotic stress: hyperphosphorylation of Hog1, nuclear localization, and expression of a monosaccharide transporter gene,\n                    <jats:italic>MST1<\/jats:italic>\n                    . Under FA stress, mRNA-containing foci are formed, as visualized by sm-FISH. Hog1 foci extensively colocalize with mRNA foci. Hog1 did not colocalize with nuclei or peroxisomes. Fragmented mitochondria, appearing upon FA exposure with a delayed time course compared to Hog1 sequestration, were mostly distinct from the Hog1 foci, with few instances of colocalization. With tagged Hog1 as an affinity purification bait, we isolated an FA-dependent sub-proteome from a subcellular fraction enriched with fluorescent foci. The identified proteins include RNA-binding proteins, translation initiation factors and mitochondrial proteins. The RRM and pumilio domain protein Puf2 was enriched, and live imaging confirmed the accumulation of a Puf2 fluorescent fusion and its colocalization with Hog1 foci following FA induction. Stress-induced sequestering of MAPK Hog1 to RNA-containing granules, together with dephosphorylation, has the potential to collectively promote survival on the plant host where stress might cause over-activation of Hog1. Conversely, FA as a host defense interferes with stress-induced Hog1 nuclear localization and downstream gene expression. The MAPK signaling mode defined by the response of Hog1 to FA is thus relevant to both host defense and pathogen survival.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013620","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:45:38Z","timestamp":1761846338000},"page":"e1013620","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cytoplasmic sequestering of a fungal stress-activated MAPK in response to a host plant phenolic acid"],"prefix":"10.1371","volume":"21","author":[{"given":"Rina","family":"Zuchman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roni","family":"Koren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Ziv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Lupu-Haber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitsan","family":"Dahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofri","family":"Levi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1558-4497","authenticated-orcid":true,"given":"Benjamin A.","family":"Horwitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"issue":"343","key":"ppat.1013620.ref001","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.2005458","article-title":"Hog1: 20 years of discovery and impact","volume":"7","author":"JL Brewster","year":"2014","journal-title":"Sci Signal"},{"issue":"12","key":"ppat.1013620.ref002","article-title":"Stress contingent changes in Hog1 pathway architecture and regulation in Candida albicans","volume":"20","author":"AM Day","year":"2024","journal-title":"PLoS Pathog"},{"issue":"11","key":"ppat.1013620.ref003","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.1111\/1462-2920.13528","article-title":"Plant phenolic acids induce programmed cell death of a fungal pathogen: MAPK signaling and survival of Cochliobolus heterostrophus","volume":"18","author":"S Shalaby","year":"2016","journal-title":"Environ Microbiol"},{"issue":"24","key":"ppat.1013620.ref004","doi-asserted-by":"crossref","first-page":"5120","DOI":"10.1111\/mec.14943","article-title":"Fungal adaptation to plant defences through convergent assembly of metabolic modules","volume":"27","author":"E Gluck-Thaler","year":"2018","journal-title":"Mol Ecol"},{"issue":"7","key":"ppat.1013620.ref005","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1038\/s41396-018-0075-3","article-title":"Specialized plant biochemistry drives gene clustering in fungi","volume":"12","author":"E Gluck-Thaler","year":"2018","journal-title":"ISME J"},{"issue":"3","key":"ppat.1013620.ref006","article-title":"Phenolic degradation by catechol dioxygenases is associated with pathogenic fungi with a necrotrophic lifestyle in the Ceratocystidaceae","volume":"12","author":"NC Soal","year":"2022","journal-title":"G3 (Bethesda)"},{"issue":"7","key":"ppat.1013620.ref007","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1094\/MPMI-01-12-0015-R","article-title":"Structure-activity relationships delineate how the maize pathogen Cochliobolus heterostrophus uses aromatic compounds as signals and metabolites","volume":"25","author":"S Shalaby","year":"2012","journal-title":"Mol Plant Microbe Interact"},{"issue":"6","key":"ppat.1013620.ref008","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1094\/MPMI-21-6-0769","article-title":"Distinct and combined roles of the MAP kinases of Cochliobolus heterostrophus in virulence and stress responses","volume":"21","author":"A Igbaria","year":"2008","journal-title":"Mol Plant Microbe Interact"},{"issue":"14","key":"ppat.1013620.ref009","doi-asserted-by":"crossref","first-page":"4826","DOI":"10.1128\/MCB.23.14.4826-4840.2003","article-title":"Combination of two activating mutations in one HOG1 gene forms hyperactive enzymes that induce growth arrest","volume":"23","author":"G Yaakov","year":"2003","journal-title":"Mol Cell Biol"},{"issue":"10","key":"ppat.1013620.ref010","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/embor.2011.154","article-title":"Sir2 histone deacetylase prevents programmed cell death caused by sustained activation of the Hog1 stress-activated protein kinase","volume":"12","author":"A Vendrell","year":"2011","journal-title":"EMBO Rep"},{"issue":"2","key":"ppat.1013620.ref011","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1128\/EC.00326-06","article-title":"Two-component response regulators Ssk1p and Skn7p additively regulate high-osmolarity adaptation and fungicide sensitivity in Cochliobolus heterostrophus","volume":"6","author":"K Izumitsu","year":"2007","journal-title":"Eukaryot Cell"},{"issue":"6","key":"ppat.1013620.ref012","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1111\/j.1365-2958.2004.04244.x","article-title":"Fungicide activity through activation of a fungal signalling pathway","volume":"53","author":"K Kojima","year":"2004","journal-title":"Mol Microbiol"},{"issue":"1","key":"ppat.1013620.ref013","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00294-019-01012-7","article-title":"The AP-1-like transcription factor ChAP1 balances tolerance and cell death in the response of the maize pathogen Cochliobolus heterostrophus to a plant phenolic","volume":"66","author":"H Simaan","year":"2020","journal-title":"Curr Genet"},{"issue":"6","key":"ppat.1013620.ref014","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/jez.2340","article-title":"Defining biological stress and stress responses based on principles of physics","volume":"333","author":"D K\u00fcltz","year":"2020","journal-title":"J Exp Zool A Ecol Integr Physiol"},{"issue":"2","key":"ppat.1013620.ref015","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3390\/jof7020083","article-title":"Developmental roles of the hog1 protein phosphatases of the maize pathogen Cochliobolus heterostrophus","volume":"7","author":"R Zuchman","year":"2021","journal-title":"J Fungi (Basel)"},{"issue":"3","key":"ppat.1013620.ref016","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.cell.2015.12.038","article-title":"ATPase-modulated stress granules contain a diverse proteome and substructure","volume":"164","author":"S Jain","year":"2016","journal-title":"Cell"},{"issue":"9","key":"ppat.1013620.ref017","article-title":"Fission yeast Puf2, a pumilio and FBF family RNA-binding protein, links stress granules to processing bodies","volume":"40","author":"W-Y Hsiao","year":"2020","journal-title":"Mol Cell Biol"},{"issue":"7","key":"ppat.1013620.ref018","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1016\/j.jmb.2020.02.020","article-title":"Distinct features of stress granule proteins predict localization in membraneless organelles","volume":"432","author":"ER Kuechler","year":"2020","journal-title":"J Mol Biol"},{"key":"ppat.1013620.ref019","doi-asserted-by":"crossref","first-page":"16019","DOI":"10.1038\/nmicrobiol.2016.19","article-title":"Fungi use the SakA (HogA) pathway for phytochrome-dependent light signalling","volume":"1","author":"Z Yu","year":"2016","journal-title":"Nat Microbiol"},{"issue":"9","key":"ppat.1013620.ref020","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.tcb.2016.05.004","article-title":"Principles and properties of stress granules","volume":"26","author":"DSW Protter","year":"2016","journal-title":"Trends Cell Biol"},{"issue":"10","key":"ppat.1013620.ref021","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.tibs.2013.07.004","article-title":"Stress granules and cell signaling: more than just a passing phase?","volume":"38","author":"N Kedersha","year":"2013","journal-title":"Trends Biochem Sci"},{"issue":"1","key":"ppat.1013620.ref022","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.209114","article-title":"Yeast Hog1 proteins are sequestered in stress granules during high-temperature stress","volume":"131","author":"K Shiraishi","year":"2018","journal-title":"J Cell Sci"},{"issue":"3","key":"ppat.1013620.ref023","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.202005102","article-title":"Stress granules display bistable dynamics modulated by Cdk","volume":"220","author":"G Yahya","year":"2021","journal-title":"J Cell Biol"},{"issue":"1","key":"ppat.1013620.ref024","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1534\/genetics.119.302376","article-title":"Insights into the role of P-bodies and stress granules in protein quality control","volume":"213","author":"R Nostramo","year":"2019","journal-title":"Genetics"},{"issue":"11","key":"ppat.1013620.ref025","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/ncb1791","article-title":"Formation of stress granules inhibits apoptosis by suppressing stress-responsive MAPK pathways","volume":"10","author":"K Arimoto","year":"2008","journal-title":"Nat Cell Biol"},{"issue":"10","key":"ppat.1013620.ref026","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2021.03.031","article-title":"Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules","volume":"184","author":"A Tulpule","year":"2021","journal-title":"Cell"},{"issue":"13","key":"ppat.1013620.ref027","doi-asserted-by":"crossref","first-page":"111879","DOI":"10.1016\/j.celrep.2022.111879","article-title":"A circadian clock translational control mechanism targets specific mRNAs to cytoplasmic messenger ribonucleoprotein granules","volume":"41","author":"KD Castillo","year":"2022","journal-title":"Cell Rep"},{"issue":"31","key":"ppat.1013620.ref028","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2203078119","article-title":"PRD-2 mediates clock-regulated perinuclear localization of clock gene RNAs within the circadian cycle of Neurospora","volume":"119","author":"BM Bartholomai","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1013620.ref029","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.90259.3","article-title":"Phosphorylation, disorder, and phase separation govern the behavior of Frequency in the fungal circadian clock","volume":"12","author":"D Tariq","year":"2024","journal-title":"Elife"},{"issue":"1","key":"ppat.1013620.ref030","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1038\/s41467-024-47761-z","article-title":"Disordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator","volume":"15","author":"MS Jankowski","year":"2024","journal-title":"Nat Commun"},{"issue":"6","key":"ppat.1013620.ref031","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/s41594-023-00999-5","article-title":"Surveying the global landscape of post-transcriptional regulators","volume":"30","author":"K Reynaud","year":"2023","journal-title":"Nat Struct Mol Biol"},{"key":"ppat.1013620.ref032","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1242\/jcs.115.16.3227","article-title":"Stressful initiations","volume":"115","author":"P Anderson","year":"2002","journal-title":"J Cell Sci"},{"issue":"5","key":"ppat.1013620.ref033","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1042\/BST0391493","article-title":"Apoptosis-like programmed cell death in the grey mould fungus Botrytis cinerea: genes and their role in pathogenicity","volume":"39","author":"N Shlezinger","year":"2011","journal-title":"Biochem Soc Trans"},{"issue":"5","key":"ppat.1013620.ref034","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1128\/EC.00277-14","article-title":"The SrkA kinase is part of the SakA mitogen-activated protein kinase interactome and regulates stress responses and development in Aspergillus nidulans","volume":"14","author":"R Jaimes-Arroyo","year":"2015","journal-title":"Eukaryot Cell"},{"issue":"3","key":"ppat.1013620.ref035","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1111\/mmi.14179","article-title":"Fungicide resistance toward fludioxonil conferred by overexpression of the phosphatase gene MoPTP2 in Magnaporthe oryzae","volume":"111","author":"S Bohnert","year":"2019","journal-title":"Mol Microbiol"},{"key":"ppat.1013620.ref036","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3389\/fcimb.2018.00128","article-title":"Mitochondrial fragmentation in Aspergillus fumigatus as early marker of granulocyte killing activity","volume":"8","author":"D Ruf","year":"2018","journal-title":"Front Cell Infect Microbiol"},{"issue":"6","key":"ppat.1013620.ref037","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.molcel.2009.11.020","article-title":"Eukaryotic stress granules: the ins and outs of translation","volume":"36","author":"JR Buchan","year":"2009","journal-title":"Mol Cell"},{"issue":"2","key":"ppat.1013620.ref038","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.molcel.2019.09.014","article-title":"Properties of stress granule and P-body proteomes","volume":"76","author":"J-Y Youn","year":"2019","journal-title":"Mol Cell"},{"issue":"20","key":"ppat.1013620.ref039","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1091\/mbc.E19-03-0172","article-title":"Conserved NDR\/LATS kinase controls RAS GTPase activity to regulate cell growth and chronological lifespan","volume":"30","author":"C Chen","year":"2019","journal-title":"Mol Biol Cell"},{"key":"ppat.1013620.ref040","article-title":"The Orb6-Sts5 axis regulates stress granule formation and heat stress response in fission yeast","author":"RN Tams","year":"2021","journal-title":"bioRxiv"},{"issue":"9","key":"ppat.1013620.ref041","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1038\/s41477-023-01499-6","article-title":"Phenolic acid-induced phase separation and translation inhibition mediate plant interspecific competition","volume":"9","author":"Z Xie","year":"2023","journal-title":"Nat Plants"},{"issue":"1","key":"ppat.1013620.ref042","first-page":"9","article-title":"Split-marker recombination for efficient targeted deletion of fungal genes","volume":"50","author":"NL Catlett","year":"2003","journal-title":"FGR"},{"issue":"26","key":"ppat.1013620.ref043","doi-asserted-by":"crossref","first-page":"12649","DOI":"10.1073\/pnas.91.26.12649","article-title":"Tagged mutations at the Tox1 locus of Cochliobolus heterostrophus by restriction enzyme-mediated integration","volume":"91","author":"S Lu","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1013620.ref044","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/978-1-0716-2871-3_14","article-title":"MycoCosm, the JGI\u2019s fungal genome portal for comparative genomic and multiomics data analyses","volume":"2605","author":"SR Ahrendt","year":"2023","journal-title":"Methods Mol Biol"},{"issue":"12","key":"ppat.1013620.ref045","article-title":"Diverse lifestyles and strategies of plant pathogenesis encoded in the genomes of eighteen Dothideomycetes fungi","volume":"8","author":"RA Ohm","year":"2012","journal-title":"PLoS Pathog"},{"key":"ppat.1013620.ref046","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-60761-611-5_1","article-title":"Protoplast transformation of filamentous fungi","volume":"638","author":"BG Turgeon","year":"2010","journal-title":"Methods Mol Biol"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1013620","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013620","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T18:43:17Z","timestamp":1762281797000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013620"}},"subtitle":[],"editor":[{"given":"Bart P.H.J.","family":"Thomma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,30]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1013620","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3197235\/v1","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,30]]}}}