Iron-dependent regulation of the divalent metal ion transporter
Iron-dependent regulation of the divalent metal ion transporter
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DOI：
10.1016/s0014-5793(01)03189-1
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发表时间：
2001-12-07
期刊：
影响因子：
3.5
通讯作者：
Hediger, MA
中科院分区：
文献类型：
--
作者：
Gunshin, H;Allerson, CR;Hediger, MA
肠道铁吸收的第一步是由H+偶联铁2+转运体介导的，称为二价阳离子转运体1/二价金属离子转运体1 (DCT1/DMT1)（也称为天然耐药相关巨噬细胞蛋白2）。十二指肠DCT1/DMT1 mRNA水平在缺铁条件下显著升高。为了研究铁依赖性DCT1/DMT1 mRNA调控的机制，我们研究了DCT1/DMT1 mRNA在不同细胞类型中的内源性表达。我们发现，只有含有铁反应元件（IRE）的形式，对应于DCT1/DMT1的两种剪接形式之一，对铁处理有反应，这种反应是细胞类型特异性的。我们还研究了假定的3'-UTR IRE与铁响应结合蛋白（IRP1和IRP2）的相互作用，发现与IRP2相比，IRP1与DCT1/DMT1-IRE结合的亲和力更高。IRP1和IRP2的差异结合也被报道为转铁蛋白受体、红系5-氨基乙酰酸合成酶和线粒体乌头酶的IREs。我们提出铁对DCT1/DMT1 mRNA的调控包括通过IRP1与转运体IRE结合的转录后调控，以及其他未知因素。(C) 2001年由Elsevier Science B.V.代表欧洲生化学会联合会出版。
The first step in intestinal iron absorption is mediated by the H+-coupled Fe2+ transporter called divalent cation transporter 1/divalent metal ion transporter 1 (DCT1/DMT1) (also known as natural resistance-associated macrophage protein 2). DCT1/DMT1 mRNA levels in the duodenum strongly increase in response to iron depletion. To study the mechanism of iron-dependent DCT1/DMT1 mRNA regulation, we investigated the endogenous expression of DCT1/DMT1 mRNA in various cell types. We found that only the iron responsive element (IRE)containing form, which corresponds to one of two splice forms of DCT1/DMT1, is responsive to iron treatment and this responsiveness was cell type specific. We also examined the interaction of the putative 3'-UTR IRE with iron responsive binding proteins (IRP1 and IRP2), and found that IRP1 binds to the DCT1/DMT1-IRE with higher affinity compared to IRP2. This differential binding of IRP1 and IRP2 was also reported for the IREs of transferrin receptors, erythroid 5-aminolevulinate synthase and mitochondrial aconitase. We propose that regulation of DCT1/DMT1 mRNA by iron involves post-transcriptional regulation through the binding of IRP1 to the transporter's IRE, as well as other as yet unknown factors. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.