The Toxic Effects of Ppz1 Overexpression Involve Nha1-Mediated Deregulation of K+ and H+ Homeostasis

0551602 - FGÚ 2022 RIV CH eng J - Journal Article
Albacar, M. - Sácká, Lenka - Calafí, C. - Velázquez, Diego - Casamayor, A. - Ariňo, J. - Zimmermannová, Olga
The Toxic Effects of Ppz1 Overexpression Involve Nha1-Mediated Deregulation of K+ and H+ Homeostasis.
Journal of Fungi. Roč. 7, č. 12 (2021), č. článku 1010. E-ISSN 2309-608X
R&D Projects: GA ČR(CZ) GA21-08985S; GA MŠMT(CZ) LTC20006
EU Projects: European Commission(XE) CA18113 - EuroMicropH
Institutional support: RVO:67985823
Keywords : Ppz1 phosphatase * cation homeostasis * Nha1 * intracellular pH * K+ transport * Saccharomyces cerevisiae
OECD category: Biochemistry and molecular biology
Impact factor: 5.724, year: 2021
Method of publishing: Open access
https://www.mdpi.com/2309-608X/7/12/1010

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.
Permanent Link: http://hdl.handle.net/11104/0326854