AGP2 encodes the major permease for high affinity polyamine import in Saccharomyces cerevisiae.
Polyamines play essential functions in many aspects of cell biology. Plasma membrane transport systems for the specific uptake of polyamines exist in most eukaryotic cells but have been very recently identified at the molecular level only in the parasite Leishmania. We now report that the high affinity polyamine permease in Saccharomyces cerevisiae is identical to Agp2p, a member of the yeast amino acid transporter family that was previously identified as a carnitine transporter. Deletion of AGP2 dramatically reduces the initial velocity of spermidine and putrescine uptake and confers strong resistance to the toxicity of exogenous polyamines, and transformation with an AGP2 expression vector restored polyamine transport in agp2delta mutants. Yeast mutants deficient in polyamine biosynthesis required >10-fold higher concentrations of exogenous putrescine to restore cell proliferation upon deletion of the AGP2 gene. Disruption of END3, a gene required for an early step of endocytosis, increased the abundance of Agp2p, an effect that was paralleled by a marked up-regulation of spermidine transport velocity. Thus, AGP2 encodes the first eukaryotic permease that preferentially uses spermidine over putrescine as a high affinity substrate and plays a central role in the uptake of polyamines in yeast.
Aouida
Mustapha
M
Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada.
Leduc
Anick
A
Poulin
Richard
R
Ramotar
Dindial
D
D000595:Amino Acid Sequence; D026905:Amino Acid Transport Systems / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001692:Biological Transport; D017931:DNA Primers; D005800:Genes, Fungal; D009997:Osmotic Pressure; D011700:Putrescine / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013095:Spermidine / Q000378:metabolism*; D027981:Symporters / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
C402286:Agp2 protein, S cerevisiae; D026905:Amino Acid Transport Systems; D017931:DNA Primers; D029701:Saccharomyces cerevisiae Proteins; D027981:Symporters; D013095:Spermidine; D011700:Putrescine