A Genomewide Screen for Tolerance to Cationic Drugs Reveals Genes Important for Potassium Homeostasis in Saccharomyces cerevisiae

Barreto, Lina; Canadell, David; Petrezsélyová, Silvia; Navarrete, Clara; Marešová, Lydie; Pérez-Valle, Jorge; Herrera, Rito; Olier, Iván; Giraldo, Jesús; Sychrová, Hana; Yenush, Lynne; Ramos, José; Ariño, Joaquı́n

doi:10.1128/ec.05029-11

Cited by 55 publications

(68 citation statements)

References 52 publications

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“…An altered K þ homeostasis was shown to affect the sensitivity to cationic drugs 28 and thus could be also related to the Cs þ phenotype of sec22D. However, in contrast to nutrient-deficient medium, the early uptake time course of Rb þ is identical for wild type and sec22D in YPD-rich medium ( Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

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Caesium accumulation in yeast and plants is selectively repressed by loss of the SNARE Sec22p/SEC22

Dräxl

Müller

et al. 2013

Nat Commun

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The non-essential cation caesium (Cs þ ) is assimilated by all organisms. Thus, anthropogenically released radiocaesium is of concern to agriculture. Cs þ accumulates owing to its chemical similarity to the potassium ion (K þ ). The apparent lack of a Cs þ -specific uptake mechanism has obstructed attempts to manipulate Cs þ accumulation without causing pleiotropic effects. Here we show that the SNARE protein Sec22p/SEC22 specifically impacts Cs þ accumulation in yeast and in plants. Loss of Saccharomyces cerevisiae Sec22p does not affect K þ homeostasis, yet halves Cs þ concentration compared with the wild type. Mathematical modelling of the uptake time course predicts a compromised vacuolar Cs þ deposition in sec22D. Biochemical fractionation confirms this and indicates a new feature of Sec22p in enhancing non-selective cation deposition. A developmentally controlled loss-of-function mutant of the orthologous Arabidopsis thaliana SEC22 phenocopies the reduced Cs þ uptake without affecting plant growth. This finding provides a new strategy to reduce radiocaesium entry into the food chain.

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Section: Discussionmentioning

confidence: 99%

“…The mitochondrial marker succinate dehydrogenase was assayed by quantifying reduced p-iodonitrotetrazolium violet 48,51 . Finally, carboxypeptidase Y and a-D-mannosidase were employed as markers for the vacuolar lumen and membrane, respectively 28,52,53 . Carboxypeptidase Y activity was based on the release of leucine from N-CBZ-L-Phe-L-Leu.…”

Section: Methodsmentioning

confidence: 99%

Caesium accumulation in yeast and plants is selectively repressed by loss of the SNARE Sec22p/SEC22

Dräxl

Müller

et al. 2013

Nat Commun

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“…Prior studies established that trk1Δtrk2Δ yeast are sensitive to the toxic cations hygromycin B (an aminoglycoside antibiotic), spermine, and tetramethylammonium (53). This phenotype arises from increased cellular uptake of the toxins in trk1Δtrk2Δ yeast because the membrane is hyperpolarized when potassium entry is limited.…”

Section: Identification Of a Romk Variant Suitable Formentioning

confidence: 99%

The endosomal trafficking factors CORVET and ESCRT suppress plasma membrane residence of the renal outer medullary potassium channel (ROMK)

Mackie

Kim

Subramanya

et al. 2018

Journal of Biological Chemistry

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“…Plates were incubated for 72 hr, and growth was recorded. For evaluation of the genetic interactions, a semiquantitative score was defined, as reported previously (Barreto et al 2011) (see also Results).…”

Section: Plasmidsmentioning

confidence: 99%

Wide-Ranging Effects of the Yeast Ptc1 Protein Phosphatase Acting Through the MAPK Kinase Mkk1

et al. 2015

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The Saccharomyces cerevisiae type 2C protein phosphatase Ptc1 is required for a wide variety of cellular functions, although only a few cellular targets have been identified. A genetic screen in search of mutations in protein kinase-encoding genes able to suppress multiple phenotypic traits caused by the ptc1 deletion yielded a single gene, MKK1, coding for a MAPK kinase (MAPKK) known to activate the cell-wall integrity (CWI) Slt2 MAPK. In contrast, mutation of the MKK1 paralog, MKK2, had a less significant effect. Deletion of MKK1 abolished the increased phosphorylation of Slt2 induced by the absence of Ptc1 both under basal and CWI pathway stimulatory conditions. We demonstrate that Ptc1 acts at the level of the MAPKKs of the CWI pathway, but only the Mkk1 kinase activity is essential for ptc1 mutants to display high Slt2 activation. We also show that Ptc1 is able to dephosphorylate Mkk1 in vitro. Our results reveal the preeminent role of Mkk1 in signaling through the CWI pathway and strongly suggest that hyperactivation of Slt2 caused by upregulation of Mkk1 is at the basis of most of the phenotypic defects associated with lack of Ptc1 function.KEYWORDS synthetic genetic interactions; cell-wall integrity pathway; protein dephosphorylation; Saccharomyces cerevisiae P ROTEIN kinases play an essential role in nearly every aspect of cell physiology, and the activity of these key players is frequently modulated by phosphorylation. Therefore, protein phosphatases (PPases) are important regulators of protein kinases and cellular homeostasis. Among them, type 2C Ser/Thr PPases constitute an evolutionarily conserved group that, in contrast to other PPase families, are monomeric enzymes apparently lacking regulatory subunits. In the yeast Saccharomyces cerevisiae, seven members (Ptc1-Ptc7) have been identified and at least partially characterized [see Arino et al. (2011) for a review].Ptc1 is the closest homolog of human Wip1, a phosphatase involved in the regulation of stress-induced and DNA damage-induced networks in diverse physiologic and pathologic conditions (Le Guezennec and Bulavin 2010;Zhu and Bulavin 2012) and by far the most widely studied yeast isoform. Both the large number of characteristic phenotypes and the specific changes in the transcriptomic profile (Gonzalez et al. 2006) derived from deletion of the gene suggest that this phosphatase is involved in a large variety of cellular processes not shared by other Ptc family members. Early evidence indicated that Ptc1 was involved in the negative regulation of the high-osmolarity glycerol (HOG) pathway (Maeda et al. 1993;Maeda et al. 1994), and subsequent work demonstrated that Ptc1 could dephosphorylate the Hog1 MAPK in vitro and in vivo (Warmka et al. 2001 interacts with the N-terminal domain of Nbp2, an SH3 domaincontaining protein that serves as an adaptor for the recruitment of Ptc1 to the Pbs2-Hog1 complex, and this interaction is necessary for Ptc1 to participate in the regulation of HOGmediated signaling (Uetz et al. 2000;Ito et al. 2001;Ma...

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A Genomewide Screen for Tolerance to Cationic Drugs Reveals Genes Important for Potassium Homeostasis in Saccharomyces cerevisiae

Cited by 55 publications

References 52 publications

Caesium accumulation in yeast and plants is selectively repressed by loss of the SNARE Sec22p/SEC22

Caesium accumulation in yeast and plants is selectively repressed by loss of the SNARE Sec22p/SEC22

The endosomal trafficking factors CORVET and ESCRT suppress plasma membrane residence of the renal outer medullary potassium channel (ROMK)

Wide-Ranging Effects of the Yeast Ptc1 Protein Phosphatase Acting Through the MAPK Kinase Mkk1

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