Iron‐dependent regulation of the divalent metal ion transporter

FEBS Letters

Allerson, Charles R.³  Kishi, Fumio⁶  Andrews, Nancy C.¹  Rofts, Andreas⁵  Hediger, Matthias A.⁵  Hentze, Matthias W.²  Rouault, Tracey A.³  Gunshin, Hiromi⁵  Rogers, Jack T.⁴  Polycarpou-Schwarz, Maria² 

[1] Hematology/Oncology Division, Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA;Heidelberg, Germany;Cell Biology and Metabolism Branch, National Institute of Child, Boston, MA, USA;Genetics and Aging Unit, Mass General Hospital and Harvard Medical School, Boston, MA, USA;Membrane Biology Program and Renal Division, Brigham and Women's Hospital and Harvard Medical School, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA;Yamaguchi University, Yamaguchi 753, Japan

关键词: Divalent cation transporter 1;    Divalent metal ion transporter 1;    Natural resistance associated macrophage protein 2;    Iron responsive element;    Iron regulatory protein;    Iron;    DCT1;    divalent cation transporter 1;    DMT1;    divalent metal ion transporter 1;    IRE;    iron responsive element;    IRP;    iron regulatory protein;   

DOI  :  10.1016/S0014-5793(01)03189-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown