{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T06:48:37Z","timestamp":1776062917082,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Science and Innovation","award":["PID2019-108045RB-I00"],"award-info":[{"award-number":["PID2019-108045RB-I00"]}]},{"name":"Spanish Ministry of Science and Innovation","award":["P20_00179"],"award-info":[{"award-number":["P20_00179"]}]},{"name":"Spanish Ministry of Science and Innovation","award":["BES-2017-082775"],"award-info":[{"award-number":["BES-2017-082775"]}]},{"name":"Spanish Ministry of Science and Innovation","award":["FP7-PEOPLE-ITN-607963"],"award-info":[{"award-number":["FP7-PEOPLE-ITN-607963"]}]},{"name":"Junta de Andaluc\u00eda","award":["PID2019-108045RB-I00"],"award-info":[{"award-number":["PID2019-108045RB-I00"]}]},{"name":"Junta de Andaluc\u00eda","award":["P20_00179"],"award-info":[{"award-number":["P20_00179"]}]},{"name":"Junta de Andaluc\u00eda","award":["BES-2017-082775"],"award-info":[{"award-number":["BES-2017-082775"]}]},{"name":"Junta de Andaluc\u00eda","award":["FP7-PEOPLE-ITN-607963"],"award-info":[{"award-number":["FP7-PEOPLE-ITN-607963"]}]},{"name":"MICINN","award":["PID2019-108045RB-I00"],"award-info":[{"award-number":["PID2019-108045RB-I00"]}]},{"name":"MICINN","award":["P20_00179"],"award-info":[{"award-number":["P20_00179"]}]},{"name":"MICINN","award":["BES-2017-082775"],"award-info":[{"award-number":["BES-2017-082775"]}]},{"name":"MICINN","award":["FP7-PEOPLE-ITN-607963"],"award-info":[{"award-number":["FP7-PEOPLE-ITN-607963"]}]},{"name":"Spanish Ministry of Education and Science","award":["PID2019-108045RB-I00"],"award-info":[{"award-number":["PID2019-108045RB-I00"]}]},{"name":"Spanish Ministry of Education and Science","award":["P20_00179"],"award-info":[{"award-number":["P20_00179"]}]},{"name":"Spanish Ministry of Education and Science","award":["BES-2017-082775"],"award-info":[{"award-number":["BES-2017-082775"]}]},{"name":"Spanish Ministry of Education and Science","award":["FP7-PEOPLE-ITN-607963"],"award-info":[{"award-number":["FP7-PEOPLE-ITN-607963"]}]},{"name":"Marie Curie ITN FUNGIBRAIN","award":["PID2019-108045RB-I00"],"award-info":[{"award-number":["PID2019-108045RB-I00"]}]},{"name":"Marie Curie ITN FUNGIBRAIN","award":["P20_00179"],"award-info":[{"award-number":["P20_00179"]}]},{"name":"Marie Curie ITN FUNGIBRAIN","award":["BES-2017-082775"],"award-info":[{"award-number":["BES-2017-082775"]}]},{"name":"Marie Curie ITN FUNGIBRAIN","award":["FP7-PEOPLE-ITN-607963"],"award-info":[{"award-number":["FP7-PEOPLE-ITN-607963"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Like many hemibiotrophic plant pathogens, the root-infecting vascular wilt fungus Fusarium oxysporum induces an increase in the pH of the surrounding host tissue. How alkalinization promotes fungal infection is not fully understood, but recent studies point towards the role of cytosolic pH (pHc) and mitogen-activated protein kinase (MAPK) signaling. In fungi, pHc is mainly controlled by the essential plasma membrane H+-ATPase Pma1. Here we created mutants of F. oxysporum lacking casein kinase 1 (Ck1), a known negative regulator of Pma1. We found that the ck1\u0394 mutants have constitutively high Pma1 activity and exhibit reduced alkalinization of the surrounding medium as well as decreased hyphal growth and conidiation. Importantly, the ck1\u0394 mutants exhibit defects in hyphal chemotropism towards plant roots and in pathogenicity on tomato plants. Thus, Ck1 is a key regulator of the development and virulence of F. oxysporum.<\/jats:p>","DOI":"10.3390\/jof8121300","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T01:46:51Z","timestamp":1671155211000},"page":"1300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Fusarium oxysporum Casein Kinase 1, a Negative Regulator of the Plasma Membrane H+-ATPase Pma1, Is Required for Development and Pathogenicity"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9179-1001","authenticated-orcid":false,"given":"Melani","family":"Mariscal","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica, Campus de Excelencia Internacional Agroalimentario ceiA3, Universidad de C\u00f3rdoba, 14014 Cordoba, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7245-9342","authenticated-orcid":false,"given":"Cristina","family":"Miguel-Rojas","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Campus de Excelencia Internacional Agroalimentario ceiA3, Universidad de C\u00f3rdoba, 14014 Cordoba, Spain"}]},{"given":"Concepci\u00f3n","family":"Hera","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Campus de Excelencia Internacional Agroalimentario ceiA3, Universidad de C\u00f3rdoba, 14014 Cordoba, Spain"}]},{"given":"T\u00e2nia R.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Campus de Excelencia Internacional Agroalimentario ceiA3, Universidad de C\u00f3rdoba, 14014 Cordoba, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5930-5763","authenticated-orcid":false,"given":"Antonio","family":"Di Pietro","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Campus de Excelencia Internacional Agroalimentario ceiA3, Universidad de C\u00f3rdoba, 14014 Cordoba, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fernandes, T.R., Segorbe, D., Prusky, D., and Di Pietro, A. (2017). How alkalinization drives fungal pathogenicity. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006621"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00294-020-01129-0","article-title":"The Rim101 pathway mediates adaptation to external alkalization and altered lipid asymmetry: Hypothesis describing the detection of distinct stresses by the Rim21 sensor protein","volume":"67","author":"Obara","year":"2021","journal-title":"Curr. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.5941\/MYCO.2011.39.4.249","article-title":"PH response pathways in fungi: Adapting to host-derived and environmental signals","volume":"39","author":"Selvig","year":"2011","journal-title":"Mycobiology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1089\/ars.2012.5062","article-title":"Virulence regulation of phytopathogenic fungi by pH","volume":"19","author":"Alkan","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1094\/MPMI.2001.14.9.1105","article-title":"Local modulation of host pH by Colletotrichum species as a mechanism to increase virulence","volume":"14","author":"Prusky","year":"2001","journal-title":"Mol. Plant Microbe Interact."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16043","DOI":"10.1038\/nmicrobiol.2016.43","article-title":"A fungal pathogen secretes plant alkalinizing peptides to increase infection","volume":"1","author":"Masachis","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1126\/science.1244454","article-title":"A peptide hormone and its receptor protein kinase regulate plant cell expansion","volume":"343","author":"Haruta","year":"2014","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-3-319-25304-6_3","article-title":"Proton transport and pH control in fungi","volume":"892","author":"Kane","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1242\/jeb.203.1.155","article-title":"Biogenesis and function of the yeast plasma-membrane H(+)-ATPase","volume":"203","author":"Ambesi","year":"2000","journal-title":"J. Exp. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/yea.3365","article-title":"The plasma membrane H(+)-ATPase, a simple polypeptide with a long history","volume":"36","author":"Palmgren","year":"2019","journal-title":"Yeast"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"35471","DOI":"10.1074\/jbc.M706094200","article-title":"Tandem phosphorylation of Ser-911 and Thr-912 at the C terminus of yeast plasma membrane H+-ATPase leads to glucose-dependent activation","volume":"282","author":"Lecchi","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0304-4157(99)00011-8","article-title":"Regulation of plasma membrane H(+)-ATPase in fungi and plants","volume":"1469","author":"Portillo","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6391","DOI":"10.1007\/s00253-015-6706-y","article-title":"Transcriptome analysis of acetic-acid-treated yeast cells identifies a large set of genes whose overexpression or deletion enhances acetic acid tolerance","volume":"99","author":"Lee","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.bbamem.2006.01.010","article-title":"Yeast protein kinase Ptk2 localizes at the plasma membrane and phosphorylates in vitro the C-terminal peptide of the H+-ATPase","volume":"1758","author":"Eraso","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7654","DOI":"10.1128\/MCB.20.20.7654-7661.2000","article-title":"Regulation of yeast H(+)-ATPase by protein kinases belonging to a family dedicated to activation of plasma membrane transporters","volume":"20","author":"Goossens","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"32064","DOI":"10.1074\/jbc.271.50.32064","article-title":"Phosphorylation of yeast plasma membrane H+-ATPase by casein kinase I","volume":"271","author":"Estrada","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.bbrc.2015.04.127","article-title":"Cu\/Zn superoxide dismutase and the proton ATPase Pma1p of Saccharomyces cerevisiae","volume":"462","author":"Baron","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e13151","DOI":"10.1111\/acel.13151","article-title":"TORC1 signaling regulates cytoplasmic pH through Sir2 in yeast","volume":"19","author":"Devare","year":"2020","journal-title":"Aging Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e09709","DOI":"10.7554\/eLife.09709","article-title":"Sir2 phosphorylation through cAMP-PKA and CK2 signaling inhibits the lifespan extension activity of Sir2 in yeast","volume":"4","author":"Kang","year":"2015","journal-title":"eLife"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1091\/mbc.E14-11-1552","article-title":"Casein kinase 1 controls the activation threshold of an \u03b1-arrestin by multisite phosphorylation of the interdomain hinge","volume":"26","author":"Herrador","year":"2015","journal-title":"Mol. Biol. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1091\/mbc.10.4.1077","article-title":"The Yck2 yeast casein kinase 1 isoform shows cell cycle-specific localization to sites of polarized growth and is required for proper septin organization","volume":"10","author":"Robinson","year":"1999","journal-title":"Mol. Biol. Cell"},{"key":"ref_22","first-page":"2870","article-title":"Casein kinase I-like protein kinases encoded by YCK1 and YCK2 are required for yeast morphogenesis","volume":"13","author":"Robinson","year":"1993","journal-title":"Mol. Cell. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1091\/mbc.e11-02-0115","article-title":"The yeast kinase Yck2 has a tripartite palmitoylation signal","volume":"22","author":"Roth","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jung, S.I., Rodriguez, N., Irrizary, J., Liboro, K., Bogarin, T., Macias, M., Eivers, E., Porter, E., Filler, S.G., and Park, H. (2017). Yeast casein kinase 2 governs morphology, biofilm formation, cell wall integrity, and host cell damage of Candida albicans. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0187721"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1128\/EC.00165-09","article-title":"Transcriptional responses of Candida albicans to epithelial and endothelial cells","volume":"8","author":"Park","year":"2009","journal-title":"Eukaryot. Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1128\/EC.05207-11","article-title":"The casein kinase I protein Cck1 regulates multiple signaling pathways and is essential for cell integrity and fungal virulence in Cryptococcus neoformans","volume":"10","author":"Wang","year":"2011","journal-title":"Eukaryot. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1080\/21505594.2019.1649588","article-title":"The casein kinase MoYck1 regulates development, autophagy, and virulence in the rice blast fungus","volume":"10","author":"Shi","year":"2019","journal-title":"Virulence"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zhu, J., Hu, D., Liu, Q., Hou, R., Xu, J.R., and Wang, G. (2022). Stage-specific genetic interaction between FgYCK1 and FgBNI4 during vegetative growth and conidiation in Fusarium graminearum. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169106"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1111\/j.1365-2958.2001.02307.x","article-title":"A MAP kinase of the vascular wilt fungus Fusarium oxysporum is essential for root penetration and pathogenesis","volume":"39","author":"Roncero","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/nature15516","article-title":"Fungal pathogen uses sex pheromone receptor for chemotropic sensing of host plant signals","volume":"527","author":"Rossi","year":"2015","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1094\/MPMI.1998.11.2.91","article-title":"Cloning, expression, and role in pathogenicity of pg1 encoding the major extracellular endopolygalacturonase of the vascular wilt pathogen Fusarium oxysporum","volume":"11","author":"Roncero","year":"1998","journal-title":"Mol. Plant Microbe Interact."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4148\/1941-4765.1150","article-title":"Split-marker recombination for efficient targeted deletion of fungal genes","volume":"50","author":"Catlett","year":"2003","journal-title":"Fungal Genet. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/0076-6879(92)16041-H","article-title":"Transformation of filamentous fungi based on hygromycin b and phleomycin resistance markers","volume":"216","author":"Punt","year":"1992","journal-title":"Methods Enzymol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1105\/tpc.110.075937","article-title":"A nitrogen response pathway regulates virulence functions in Fusarium oxysporum via the protein kinase TOR and the bZIP protein MeaB","volume":"22","author":"Rispail","year":"2010","journal-title":"Plant Cell"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kahm, M., Navarrete, C., Llopis-Torregrosa, V., Herrera, R., Barreto, L., Yenush, L., Ari\u00f1o, J., Ramos, J., and Kschischo, M. (2012). Potassium starvation in yeast: Mechanisms of homeostasis revealed by mathematical modeling. PLoS Comput. Biol., 8.","DOI":"10.1371\/journal.pcbi.1002548"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-0716-1795-3_9","article-title":"In vivo monitoring of cytosolic pH using the ratiometric pH sensor pHluorin","volume":"2391","author":"Fernandes","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41467-022-28293-w","article-title":"Cyclic AMP signalling and glucose metabolism mediate pH taxis by African trypanosomes","volume":"13","author":"Shaw","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_38","first-page":"1","article-title":"Total protein extraction with TCA-acetone","volume":"355","author":"Damerval","year":"2007","journal-title":"Methods Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1111\/nph.16085","article-title":"NADPH oxidase regulates chemotropic growth of the fungal pathogen Fusarium oxysporum towards the host plant","volume":"224","author":"Nordzieke","year":"2019","journal-title":"New Phytol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0014-5793(89)81498-X","article-title":"A synthetic peptide substrate specific for casein kinase I","volume":"259","author":"Agostinis","year":"1989","journal-title":"FEBS Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1111\/j.1432-1033.1994.tb19037.x","article-title":"Phosphorylation of synthetic fragments of inhibitor-2 of protein phosphatase-1 by casein kinase-1 and -2. Evidence that phosphorylated residues are not strictly required for efficient targeting by casein kinase-1","volume":"223","author":"Marin","year":"1994","journal-title":"Eur. J. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s002030000185","article-title":"Individual cells of Saccharomyces cerevisiae and Zygosaccharomyces bailii exhibit different short-term intracellular pH responses to acetic acid","volume":"174","author":"Arneborg","year":"2000","journal-title":"Arch. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Fernandes, T.R., Mariscal, M., Serrano, A., Segorbe, D., Fern\u00e1ndez-Acero, T., Mart\u00edn, H., Turr\u00e0, D., and Di Pietro, A. (2022). Cytosolic pH controls fungal MAPK signaling and pathogenicity. bioRxiv.","DOI":"10.1101\/2022.10.23.513408"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4518","DOI":"10.1038\/ncomms5518","article-title":"Germination and infectivity of microconidia in the rice blast fungus Magnaporthe oryzae","volume":"5","author":"Zhang","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s00253-016-7898-5","article-title":"Overexpression of PMA1 enhances tolerance to various types of stress and constitutively activates the SAPK pathways in Saccharomyces cerevisiae","volume":"101","author":"Lee","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1042\/BST0391538","article-title":"Achievements and perspectives in yeast acetic acid-induced programmed cell death pathways","volume":"39","author":"Guaragnella","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7743","DOI":"10.1074\/jbc.A117.710470","article-title":"Vacuolar and plasma membrane proton pumps collaborate to achieve cytosolic pH homeostasis in yeast","volume":"292","author":"Kane","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1093\/emboj\/21.5.920","article-title":"The Ppz protein phosphatases are key regulators of K+ and pH homeostasis: Implications for salt tolerance, cell wall integrity and cell cycle progression","volume":"21","author":"Yenush","year":"2002","journal-title":"EMBO J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8683","DOI":"10.1128\/MCB.25.19.8683-8692.2005","article-title":"pH-Responsive, posttranslational regulation of the Trk1 potassium transporter by the type 1-related Ppz1 phosphatase","volume":"25","author":"Yenush","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5264","DOI":"10.1038\/s41467-020-18994-5","article-title":"A bacterial endophyte exploits chemotropism of a fungal pathogen for plant colonization","volume":"11","author":"Palmieri","year":"2020","journal-title":"Nat. Commun."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/8\/12\/1300\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:42:08Z","timestamp":1760146928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/8\/12\/1300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,15]]},"references-count":50,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["jof8121300"],"URL":"https:\/\/doi.org\/10.3390\/jof8121300","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,15]]}}}