Abstract
Ypi1 was discovered as an essential protein able to act as a regulatory subunit of the Saccharomyces cerevisiae type 1 protein phosphatase Glc7 and play a key role in mitosis. We show here that partial depletion of Ypi1 causes lithium sensitivity and that high levels of this protein confer a lithium-tolerant phenotype to yeast cells. Remarkably, this phenotype was independent of the role of Ypi1 as a Glc7 regulatory subunit. Lithium tolerance in cells overexpressing Ypi1 was caused by a combination of increased efflux of lithium, mediated by augmented expression of the alkaline cation ATPase ENA1, and decreased lithium influx through the Trk1,2 high-affinity potassium transporters. Deletion of CNB1, encoding the regulatory subunit of the calcineurin phosphatase, blocked Ypi1-induced expression of ENA1, normalized Li(+) fluxes, and abolished the Li(+) hypertolerant phenotype of Ypi1-overexpressing cells. These results point to a complex role of Ypi1 on the regulation of cation homeostasis, largely mediated by the calcineurin phosphatase.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptation, Physiological
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Calcineurin / genetics
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Calcineurin / metabolism*
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Cation Transport Proteins / genetics
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Cation Transport Proteins / metabolism
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Enzyme Activation
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Gene Expression Regulation, Enzymologic
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Gene Expression Regulation, Fungal
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Genes, Fungal
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Homeostasis
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Lithium Chloride / metabolism
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Lithium Chloride / pharmacology
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Phenotype
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Phosphoric Monoester Hydrolases / metabolism
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Plasmids / genetics
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Plasmids / metabolism
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae / physiology
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Sodium-Potassium-Exchanging ATPase / genetics
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Sodium-Potassium-Exchanging ATPase / metabolism
Substances
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Cation Transport Proteins
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ENA1 protein, S cerevisiae
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Intracellular Signaling Peptides and Proteins
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Saccharomyces cerevisiae Proteins
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TRK2 protein, S cerevisiae
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Ypi1 protein, S cerevisiae
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TRK1 protein, S cerevisiae
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calcineurin phosphatase
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Calcineurin
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Phosphoric Monoester Hydrolases
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Sodium-Potassium-Exchanging ATPase
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Lithium Chloride