The Toxic Effects of Ppz1 Overexpression Involve Nha1-Mediated Deregulation of K+ and H+ Homeostasis
Albacar, Marcel (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Sacka, Lenka (Institute of Physiology of the Czech Academy of Sciences. Laboratory of Membrane Transport)
Calafí, Carlos (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Velázquez, Diego (Institute of Physiology of the Czech Academy of Sciences. Laboratory of Membrane Transport)
Casamayor Gracia, Antonio (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Ariño Carmona, Joaquín (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Zimmermannova, Olga (Institute of Physiology of the Czech Academy of Sciences. Laboratory of Membrane Transport)
Data: |
2021 |
Resum: |
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. |
Ajuts: |
Agencia Estatal de Investigación BFU2017-82574-P
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Drets: |
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Llengua: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Matèria: |
Ppz1 phosphatase ;
Cation homeostasis ;
Nha1 ;
Intracellular pH ;
K+ transport ;
Saccharomyces cerevisiae |
Publicat a: |
Journal of Fungi, Vol. 7, Issue 12 (December 2021) , art. 1010, ISSN 2309-608X |
DOI: 10.3390/jof7121010
PMID: 34946993
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Registre creat el 2022-02-18, darrera modificació el 2024-01-30