title: Agp2, a member of the yeast amino acid permease family, positively regulates polyamine transport at the transcriptional level.
abstract: Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3Δ nor sam3Δ single mutant is defective in polyamine transport, while the dur3Δ sam3Δ double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2Δ mutant. Studies of Agp2 localization indicate that in the double mutant dur3Δ sam3Δ, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport.
authors.affiliation: Center for Desert Agriculture, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia. Mustapha.aouida@kaust.edu.sa
authors.forename: Mustapha
authors.initials: M
authors.lastname: Aouida
authors.forename: Marta
authors.initials: M
authors.lastname: Rubio-Texeira
authors.forename: Marta
authors.initials: M
authors.lastname: Rubio Texeira
authors.forename: Johan M
authors.initials: JM
authors.lastname: Thevelein
authors.forename: Richard
authors.initials: R
authors.lastname: Poulin
authors.forename: Dindial
authors.initials: D
authors.lastname: Ramotar
mesh_terms: D026905:Amino Acid Transport Systems / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D001692:Biological Transport; D002331:Carnitine / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D026901:Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D058977:Molecular Sequence Annotation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013095:Spermidine / Q000378:metabolism*; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C402286:Agp2 protein, S cerevisiae; D026905:Amino Acid Transport Systems; C515373:DUR3 protein, S cerevisiae; D026901:Membrane Transport Proteins; C429746:SAM3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D027981:Symporters; C065637:choline transporter; C490216:SKY1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D002331:Carnitine; D013095:Spermidine