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Iron‐dependent regulation of the divalent metal ion transporter
Author(s) -
Gunshin Hiromi,
Allerson Charles R.,
Polycarpou-Schwarz Maria,
Rofts Andreas,
Rogers Jack T.,
Kishi Fumio,
Hentze Matthias W.,
Rouault Tracey A.,
Andrews Nancy C.,
Hediger Matthias A.
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)03189-1
Subject(s) - dmt1 , transporter , chemistry , transferrin receptor , transferrin , biochemistry , receptor , divalent , microbiology and biotechnology , biophysics , biology , gene , organic chemistry
The first step in intestinal iron absorption is mediated by the H + ‐coupled Fe 2+ 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.