title: A genomewide screen for tolerance to cationic drugs reveals genes important for potassium homeostasis in Saccharomyces cerevisiae.
abstract: Potassium homeostasis is crucial for living cells. In the yeast Saccharomyces cerevisiae, the uptake of potassium is driven by the electrochemical gradient generated by the Pma1 H(+)-ATPase, and this process represents a major consumer of the gradient. We considered that any mutation resulting in an alteration of the electrochemical gradient could give rise to anomalous sensitivity to any cationic drug independently of its toxicity mechanism. Here, we describe a genomewide screen for mutants that present altered tolerance to hygromycin B, spermine, and tetramethylammonium. Two hundred twenty-six mutant strains displayed altered tolerance to all three drugs (202 hypersensitive and 24 hypertolerant), and more than 50% presented a strong or moderate growth defect at a limiting potassium concentration (1 mM). Functional groups such as protein kinases and phosphatases, intracellular trafficking, transcription, or cell cycle and DNA processing were enriched. Essentially, our screen has identified a substantial number of genes that were not previously described to play a direct or indirect role in potassium homeostasis. A subset of 27 representative mutants were selected and subjected to diverse biochemical tests that, in some cases, allowed us to postulate the basis for the observed phenotypes.
authors: Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès 08193, Barcelona, Spain.
authors: Lina
authors: L
authors: Barreto
authors: David
authors: D
authors: Canadell
authors: Silvia
authors: S
authors: Petrezsélyová
authors: Clara
authors: C
authors: Navarrete
authors: Lydie
authors: L
authors: Maresová
authors: Jorge
authors: J
authors: Peréz-Valle
authors: Rito
authors: R
authors: Herrera
authors: Iván
authors: I
authors: Olier
authors: Jesús
authors: J
authors: Giraldo
authors: Hana
authors: H
authors: Sychrová
authors: Lynne
authors: L
authors: Yenush
authors: José
authors: J
authors: Ramos
authors: Joaquín
authors: J
authors: Ariño
mesh_terms: D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis; D006921:Hygromycin B / Q000494:pharmacology; D008564:Membrane Potentials; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011188:Potassium / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology
chemical_list: D027682:Cation Transport Proteins; D000644:Quaternary Ammonium Compounds; D029701:Saccharomyces cerevisiae Proteins; C068664:TRK1 protein, S cerevisiae; D013096:Spermine; D006921:Hygromycin B; C092477:PMA1 protein, S cerevisiae; D006180:Proton-Translocating ATPases; C027917:tetramethylammonium; D011188:Potassium