AGP2 encodes the major permease for high affinity polyamine import in Saccharomyces cerevisiae
AGP2 encodes the major permease for high affinity polyamine import in Saccharomyces cerevisiae
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DOI：
10.1074/jbc.m503071200
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发表时间：
2005-06-24
影响因子：
4.8
通讯作者：
Ramotar, D
中科院分区：
文献类型：
--
作者：
Aouida, M;Leduc, A;Ramotar, D
多胺在细胞生物学的许多方面发挥着重要作用。大多数真核细胞中都存在用于特异性摄取多胺的质膜转运系统，但最近仅在寄生虫利什曼原虫中在分子水平上得到了鉴定。我们现在报道，酿酒酵母中的高亲和力多胺通透酶与 Agp2p 相同，Agp2p 是酵母氨基酸转运蛋白家族的成员，之前被鉴定为肉碱转运蛋白。 AGP2的缺失显着降低了亚精胺和腐胺摄取的初始速度，并赋予了对外源多胺毒性的强大抵抗力，并且用AGP2表达载体进行的转化恢复了agp2 Delta突变体中的多胺转运。缺乏多胺生物合成的酵母突变体需要高于 10 倍浓度的外源腐胺，才能在 AGP2 基因缺失后恢复细胞增殖。 END3（内吞作用早期所需的基因）的破坏增加了 Agp2p 的丰度，这种效应与亚精胺转运速度的显着上调同时发生。因此，AGP2编码第一个真核通透酶，它优先使用亚精胺而不是腐胺作为高亲和力底物，并在酵母吸收多胺中发挥核心作用。
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 agp2 Delta 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.