Iron‐dependent regulation of the divalent metal ion transporter

FEBS Letters - Tập 509 Số 2 - Trang 309-316 - 2001
Hiromi Gunshin1,2, Charles Allerson3, Maria Polycarpou‐Schwarz4, Andreas Rofts2, Jack T. Rogers5, Fumio Kishi6, Matthias W. Hentze4, Tracey A. Rouault3, Nancy C. Andrews1,7, Matthias A. Hediger2
1Hematology/Oncology Division, Children’s Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
2Membrane 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
3Cell Biology and Metabolism Branch, National Institute of Child, Boston, MA, USA
4Heidelberg, Germany
5Genetics and Aging Unit, Mass General Hospital and Harvard Medical School, Boston, MA, USA
6Yamaguchi University, Yamaguchi 753, Japan
7Howard Hughes Medical Institute, Boston, MA, USA

Tóm tắt

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.

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Tài liệu tham khảo

10.1042/bj2190001

10.1074/jbc.272.31.19095

Brittenham G.M. (1994) The red cell cycle in: Iron Metabolism in Health and Disease (Brock J.H. Halliday J.W. Pippard M.J. and Powell L.W. Eds.) W.B. Saunders London.

10.1038/41343

10.1038/ng0897-383

10.1182/blood.V93.12.4406

10.1006/bcmd.1998.0186

10.1074/jbc.M001478200

10.1002/j.1460-2075.1994.tb06466.x

10.1126/science.2452485

10.1073/pnas.84.23.8478

10.1002/j.1460-2075.1991.tb07715.x

10.1002/j.1460-2075.1991.tb07716.x

10.1126/science.3685996

10.1074/jbc.270.51.30781

10.1016/0003-9861(92)90287-7

10.1016/S1097-2765(00)80425-6

10.1038/35001596

10.1074/jbc.M000713200

10.1074/jbc.274.37.26439

10.1074/jbc.273.37.23637

10.1002/j.1460-2075.1989.tb08544.x

10.1016/0092-8674(89)90851-9

10.1016/S0016-5085(99)70244-1

10.1056/NEJM199912233412607

10.1182/blood.V96.13.4020

10.1073/pnas.96.6.3143

10.1016/S0140-6736(98)11179-0

10.1046/j.1432-1327.1999.00155.x

10.1016/0016-5085(95)90026-8

10.1016/S0161-5890(97)00110-7

10.1046/j.1432-1327.1999.00447.x

10.1038/5979

10.1016/S0021-9258(19)74253-7

10.1074/jbc.M010295200

10.1182/blood.V92.6.2157

10.1074/jbc.271.20.12017

10.1074/jbc.M002354200

10.1073/pnas.93.9.4345

Rolfs A. Bonkovsky H.L. Kohlroser J.G. McNeal K. Sharma A. Berger U.V. and Hediger M.A. (2001) Am. J. Physiol. Gastrointest. Liver Physiol. in press.

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FEBS Letters

Tập 509 Số 2

309-316

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