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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 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The Toxic Effects of Ppz1 Overexpression Involve Nha1-Mediated Deregulation of K+ and H+ Homeostasis Author(s) 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, ORCIDArticle number 1010 Source Title Journal of Fungi. - : MDPI
Roč. 7, č. 12 (2021)Number of pages 17 s. Language eng - English Country CH - Switzerland Keywords Ppz1 phosphatase ; cation homeostasis ; Nha1 ; intracellular pH ; K+ transport ; Saccharomyces cerevisiae OECD category Biochemistry and molecular biology R&D Projects GA21-08985S GA ČR - Czech Science Foundation (CSF) LTC20006 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000737637700001 EID SCOPUS 85123016229 DOI 10.3390/jof7121010 Annotation 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. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2022 Electronic address https://www.mdpi.com/2309-608X/7/12/1010
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