title: Saccharomyces cerevisiae multidrug resistance transporter Qdr2 is implicated in potassium uptake, providing a physiological advantage to quinidine-stressed cells.
abstract: The QDR2 gene of Saccharomyces cerevisiae encodes a putative plasma membrane drug:H(+) antiporter that confers resistance against quinidine, barban, bleomycin, and cisplatin. This work provides experimental evidence of defective K(+) (Rb(+)) uptake in the absence of QDR2. The direct involvement of Qdr2p in K(+) uptake is reinforced by the fact that increased K(+) (Rb(+)) uptake due to QDR2 expression is independent of the Trk1p/Trk2p system. QDR2 expression confers a physiological advantage for the yeast cell during the onset of K(+) limited growth, due either to a limiting level of K(+) in the growth medium or to the presence of quinidine. This drug decreases the K(+) uptake rate and K(+) accumulation in the yeast cell, especially in the Deltaqdr2 mutant. Qdr2p also helps to sustain the decrease of intracellular pH in quinidine-stressed cells in growth medium at pH 5.5 by indirectly promoting H(+) extrusion affected by the drug. The results are consistent with the hypothesis that Qdr2p may also couple K(+) movement with substrate export, presumably with quinidine. Other clues to the biological role of QDR2 in the yeast cell come from two additional lines of experimental evidence. First, QDR2 transcription is activated under nitrogen (NH(4)(+)) limitation or when the auxotrophic strain examined enters stationary phase due to leucine limitation, this regulation being dependent on general amino acid control by Gcn4p. Second, the amino acid pool is higher in Deltaqdr2 cells than in wild-type cells, indicating that QDR2 expression is, directly or indirectly, involved in amino acid homeostasis.
authors.affiliation: IBB-Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Vargas
authors.forename: Raúl
authors.initials: R
authors.lastname: García-Salcedo
authors.forename: Sandra
authors.initials: S
authors.lastname: Tenreiro
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Teixeira
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Fernandes
authors.forename: José
authors.initials: J
authors.lastname: Ramos
authors.forename: Isabel
authors.initials: I
authors.lastname: Sá-Correia
mesh_terms: D001692:Biological Transport; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D026141:Drug Resistance, Multiple, Fungal / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D026901:Membrane Transport Proteins / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D011522:Protons; D011802:Quinidine / Q000494:pharmacology*; D012413:Rubidium / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D027682:Cation Transport Proteins; D026901:Membrane Transport Proteins; D011522:Protons; C489155:Qdr2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C085258:TRK2 protein, S cerevisiae; C068664:TRK1 protein, S cerevisiae; D011802:Quinidine; D012413:Rubidium; D011188:Potassium