Role of the Transporter Regulator Protein (RS1) in the Modulation of Concentrative Nucleoside Transporters (CNTs) in Epithelia
Role of the Transporter Regulator Protein (RS1) in the Modulation of Concentrative Nucleoside Transporters (CNTs) in Epithelia
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DOI：
10.1124/mol.111.076992
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发表时间：
2012-07-01
影响因子：
3.6
通讯作者：
Pastor-Anglada, Marcal
中科院分区：
文献类型：
--
作者：
Errasti-Murugarren, Ekaitz;Fernandez-Calotti, Paula;Pastor-Anglada, Marcal
SLC28 基因编码三种质膜转运蛋白，即人类集中核苷转运蛋白 (CNT)1、CNT2 和 CNT3，所有这些蛋白都与天然核苷以及用于癌症、病毒和炎症性疾病化疗的各种核苷类似物的摄取有关。决定它们向质膜运输的机制尚不清楚，尽管这最终可能成为治疗干预的目标。转运蛋白调节剂 RS1 最初被确定为高亲和力、Na+偶联、葡萄糖转运蛋白钠依赖性葡萄糖协同转运蛋白 1 的短期转录后调节剂，在本研究中被评估为协调调节人类 CNT 型蛋白膜插入的候选者。通过对哺乳动物细胞、非洲爪蟾卵母细胞和 RS1 缺失小鼠的研究，提供了 RS1 下调该蛋白家族三个成员（CNT1、CNT2 和 CNT3）在质膜上的定位和活性的证据，这表明了上皮细胞以及可能在其他表达 RS1 的细胞类型中协调调节核苷摄取能力的生化基础。
SLC28 genes encode three plasma membrane transporter proteins, human concentrative nucleoside transporter (CNT)1, CNT2, and CNT3, all of which are implicated in the uptake of natural nucleosides and a variety of nucleoside analogs used in the chemotherapy of cancer and viral and inflammatory diseases. Mechanisms determining their trafficking toward the plasma membrane are not well known, although this might eventually become a target for therapeutic intervention. The transporter regulator RS1, which was initially identified as a short-term, post-transcriptional regulator of the high-affinity, Na+-coupled, glucose transporter sodium-dependent glucose cotransporter 1, was evaluated in this study as a candidate for coordinate regulation of membrane insertion of human CNT-type proteins. With a combination of studies with mammalian cells, Xenopus laevis oocytes, and RS1-null mice, evidence that RS1 down-regulates the localization and activity at the plasma membrane of the three members of this protein family (CNT1, CNT2, and CNT3) is provided, which indicates the biochemical basis for coordinate regulation of nucleoside uptake ability in epithelia and probably in other RS1-expressing cell types.