Agp2, a member of the yeast amino acid permease family, positively regulates polyamine transport at the transcriptional level.

Agp2, a member of the yeast amino acid permease family, positively regulates polyamine transport at the transcriptional level.
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DOI:
10.1371/journal.pone.0065717
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Ramotar D
Ramotar D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Aouida M;Rubio-Texeira M;Thevelein JM;Poulin R;Ramotar D

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Agp2是酿酒酵母氨基酸转运蛋白家族的一种质膜蛋白,参与多种底物的高亲和力摄取,包括左旋肉碱和多胺。两种高亲和多胺渗透物Dur3和Sam3的发现促使我们研究Agp2是直接运输多胺还是作为调节剂。在此,我们发现dur3Δ和sam3Δ单突变体在多胺运输方面都没有缺陷,而dur3Δ sam3Δ双突变体在多胺摄取方面表现出急剧下降,并且对多胺毒性的抗性增加,这与agp2Δ突变体相似。对Agp2定位的研究表明,在双突变体dur3Δ sam3Δ中,Agp2- gfp保持质膜定位,尽管多胺的转运强烈减少。我们进一步证明,Agp2控制几种转运基因的表达,包括DUR3和SAM3,肉碱转运蛋白HNM1和几种己糖,核苷和维生素渗透酶基因,除了SKY1编码一个SR激酶,积极调节低亲和力多胺摄取。此外,基因表达分析清楚地表明,Agp2是其他生物过程的强正调节因子。总的来说,我们的数据表明Agp2可能对环境信号做出反应,从而调节包括参与多胺运输的基因在内的几种基因的表达。
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.
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