title: Modulation of yeast alkaline cation tolerance by Ypi1 requires calcineurin.
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.
authors.affiliation: Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain.
authors.forename: Maribel
authors.initials: M
authors.lastname: Marquina
authors.forename: Asier
authors.initials: A
authors.lastname: González
authors.forename: Lina
authors.initials: L
authors.lastname: Barreto
authors.forename: Samuel
authors.initials: S
authors.lastname: Gelis
authors.forename: Iván
authors.initials: I
authors.lastname: Muñoz
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruiz
authors.forename: Mari Carmen
authors.initials: MC
authors.lastname: Alvarez
authors.forename: José
authors.initials: J
authors.lastname: Ramos
authors.forename: Joaquín
authors.initials: J
authors.lastname: Ariño
mesh_terms: D000222:Adaptation, Physiological; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006706:Homeostasis; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D018021:Lithium Chloride / Q000378:metabolism / Q000494:pharmacology; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; C086375:ENA1 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; C085258:TRK2 protein, S cerevisiae; C480163:Ypi1 protein, S cerevisiae; C068664:TRK1 protein, S cerevisiae; C120817:calcineurin phosphatase; D019703:Calcineurin; D010744:Phosphoric Monoester Hydrolases; D000254:Sodium-Potassium-Exchanging ATPase; D018021:Lithium Chloride