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

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Institut de Biotecnologia i Biomedicina & Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain
2
Laboratory of Membrane Transport, Institute of Physiology of the Czech Academy of Sciences, 142220 Prague, Czech Republic
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Authors to whom correspondence should be addressed.
Academic Editor: Sotiris Amillis
J. Fungi 2021, 7(12), 1010; https://doi.org/10.3390/jof7121010
Received: 19 October 2021 / Revised: 18 November 2021 / Accepted: 23 November 2021 / Published: 25 November 2021
(This article belongs to the Section Fungal Cell Biology, Metabolism and Physiology)
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. View Full-Text
Keywords: Ppz1 phosphatase; cation homeostasis; Nha1; intracellular pH; K+ transport; Saccharomyces cerevisiae Ppz1 phosphatase; cation homeostasis; Nha1; intracellular pH; K+ transport; Saccharomyces cerevisiae
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MDPI and ACS Style

Albacar, M.; Sacka, L.; Calafí, C.; Velázquez, D.; Casamayor, A.; Ariño, J.; Zimmermannova, O. The Toxic Effects of Ppz1 Overexpression Involve Nha1-Mediated Deregulation of K+ and H+ Homeostasis. J. Fungi 2021, 7, 1010. https://doi.org/10.3390/jof7121010

AMA Style

Albacar M, Sacka L, Calafí C, Velázquez D, Casamayor A, Ariño J, Zimmermannova O. The Toxic Effects of Ppz1 Overexpression Involve Nha1-Mediated Deregulation of K+ and H+ Homeostasis. Journal of Fungi. 2021; 7(12):1010. https://doi.org/10.3390/jof7121010

Chicago/Turabian Style

Albacar, Marcel, Lenka Sacka, Carlos Calafí, Diego Velázquez, Antonio Casamayor, Joaquín Ariño, and Olga Zimmermannova. 2021. "The Toxic Effects of Ppz1 Overexpression Involve Nha1-Mediated Deregulation of K+ and H+ Homeostasis" Journal of Fungi 7, no. 12: 1010. https://doi.org/10.3390/jof7121010

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