Iron-dependent regulation of the divalent metal ion transporter.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gunshin, H; Allerson, CR; Polycarpou-Schwarz, M; Rofts, A; Rogers, JT; Kishi, F; Hentze, MW; Rouault, TA; Andrews, NC; Hediger, MA

Published Date

  • December 7, 2001

Published In

Volume / Issue

  • 509 / 2

Start / End Page

  • 309 - 316

PubMed ID

  • 11741608

Pubmed Central ID

  • 11741608

International Standard Serial Number (ISSN)

  • 0014-5793

Digital Object Identifier (DOI)

  • 10.1016/s0014-5793(01)03189-1

Language

  • eng

Conference Location

  • England