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The Toxic Effects of Ppz1 Overexpression Involve Nha1-Mediated Deregulation of K+ and H+ Homeostasis
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SYSNO ASEP 0551602 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název The Toxic Effects of Ppz1 Overexpression Involve Nha1-Mediated Deregulation of K+ and H+ Homeostasis Tvůrce(i) Albacar, M. (ES)
Sácká, Lenka (FGU-C)
Calafí, C. (ES)
Velázquez, Diego (FGU-C)
Casamayor, A. (ES)
Ariňo, J. (ES)
Zimmermannová, Olga (FGU-C) RID, ORCIDČíslo článku 1010 Zdroj.dok. Journal of Fungi. - : MDPI
Roč. 7, č. 12 (2021)Poč.str. 17 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova Ppz1 phosphatase ; cation homeostasis ; Nha1 ; intracellular pH ; K+ transport ; Saccharomyces cerevisiae Obor OECD Biochemistry and molecular biology CEP GA21-08985S GA ČR - Grantová agentura ČR LTC20006 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000737637700001 EID SCOPUS 85123016229 DOI 10.3390/jof7121010 Anotace The alteration of the fine-tuned balance of phospho/dephosphorylation reactions in the cell often results in functional disturbance. In the yeast Saccharomyces cerevisiae, the overexpression of Ser/Thr phosphatase Ppz1 drastically blocks cell proliferation, with a profound change in the transcriptomic and phosphoproteomic profiles. While the deleterious effect on growth likely derives from the alteration of multiple targets, the precise mechanisms are still obscure. Ppz1 is a negative effector of potassium influx. However, we show that the toxic effect of Ppz1 overexpression is unrelated to the Trk1/2 high-affinity potassium importers. Cells overexpressing Ppz1 exhibit decreased K+ content, increased cytosolic acidification, and fail to properly acidify the medium. These effects, as well as the growth defect, are counteracted by the deletion of NHA1 gene, which encodes a plasma membrane Na+, K+/H+ antiporter. The beneficial effect of a lack of Nha1 on the growth vanishes as the pH of the medium approaches neutrality, is not eliminated by the expression of two non-functional Nha1 variants (D145N or D177N), and is exacerbated by a hyperactive Nha1 version (S481A). All our results show that high levels of Ppz1 overactivate Nha1, leading to an excessive entry of H+ and efflux of K+, which is detrimental for growth. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2022 Elektronická adresa https://www.mdpi.com/2309-608X/7/12/1010
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