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Iron-dependent regulation of the divalent metal ion transporter.

Publication ,  Journal Article
Gunshin, H; Allerson, CR; Polycarpou-Schwarz, M; Rofts, A; Rogers, JT; Kishi, F; Hentze, MW; Rouault, TA; Andrews, NC; Hediger, MA
Published in: FEBS letters
December 2001

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.

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Published In

FEBS letters

DOI

EISSN

1873-3468

ISSN

0014-5793

Publication Date

December 2001

Volume

509

Issue

2

Start / End Page

309 / 316

Related Subject Headings

  • Regulatory Sequences, Nucleic Acid
  • RNA-Binding Proteins
  • RNA Processing, Post-Transcriptional
  • Protein Binding
  • Nucleic Acid Conformation
  • Iron-Sulfur Proteins
  • Iron-Regulatory Proteins
  • Iron-Binding Proteins
  • Iron Regulatory Protein 2
  • Iron Regulatory Protein 1
 

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Gunshin, H., Allerson, C. R., Polycarpou-Schwarz, M., Rofts, A., Rogers, J. T., Kishi, F., … Hediger, M. A. (2001). Iron-dependent regulation of the divalent metal ion transporter. FEBS Letters, 509(2), 309–316. https://doi.org/10.1016/s0014-5793(01)03189-1
Gunshin, H., C. R. Allerson, M. Polycarpou-Schwarz, A. Rofts, J. T. Rogers, F. Kishi, M. W. Hentze, T. A. Rouault, N. C. Andrews, and M. A. Hediger. “Iron-dependent regulation of the divalent metal ion transporter.FEBS Letters 509, no. 2 (December 2001): 309–16. https://doi.org/10.1016/s0014-5793(01)03189-1.
Gunshin H, Allerson CR, Polycarpou-Schwarz M, Rofts A, Rogers JT, Kishi F, et al. Iron-dependent regulation of the divalent metal ion transporter. FEBS letters. 2001 Dec;509(2):309–16.
Gunshin, H., et al. “Iron-dependent regulation of the divalent metal ion transporter.FEBS Letters, vol. 509, no. 2, Dec. 2001, pp. 309–16. Epmc, doi:10.1016/s0014-5793(01)03189-1.
Gunshin H, Allerson CR, Polycarpou-Schwarz M, Rofts A, Rogers JT, Kishi F, Hentze MW, Rouault TA, Andrews NC, Hediger MA. Iron-dependent regulation of the divalent metal ion transporter. FEBS letters. 2001 Dec;509(2):309–316.
Journal cover image

Published In

FEBS letters

DOI

EISSN

1873-3468

ISSN

0014-5793

Publication Date

December 2001

Volume

509

Issue

2

Start / End Page

309 / 316

Related Subject Headings

  • Regulatory Sequences, Nucleic Acid
  • RNA-Binding Proteins
  • RNA Processing, Post-Transcriptional
  • Protein Binding
  • Nucleic Acid Conformation
  • Iron-Sulfur Proteins
  • Iron-Regulatory Proteins
  • Iron-Binding Proteins
  • Iron Regulatory Protein 2
  • Iron Regulatory Protein 1