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Cloning and characterization of a mammalian proton-coupled metal-ion transporter

Author

Listed:
  • Hiromi Gunshin

    (Brigham & Women's Hospital and Harvard Medical School)

  • Bryan Mackenzie

    (Brigham & Women's Hospital and Harvard Medical School)

  • Urs V. Berger

    (Brigham & Women's Hospital and Harvard Medical School)

  • Yoshimi Gunshin

    (Brigham & Women's Hospital and Harvard Medical School)

  • Michael F. Romero

    (Yale University)

  • Walter F. Boron

    (Yale University)

  • Stephan Nussberger

    (Brigham & Women's Hospital and Harvard Medical School)

  • John L. Gollan

    (Brigham & Women's Hospital)

  • Matthias A. Hediger

    (Brigham & Women's Hospital and Harvard Medical School
    Harvard Medical School)

Abstract

Metal ions are essential cofactors for a wealth of biological processes, including oxidative phosphorylation, gene regulation and free-radical homeostasis. Failure to maintain appropriate levels of metal ions in humans is a feature of hereditary haemochromatosis1, disorders of metal-ion deficiency, and certain neurodegenerative diseases2. Despite their pivotal physiological roles, however, there is no molecular information on how metal ions are actively absorbed by mammalian cells. We have now identified a new metal-ion transporter in the rat, DCT1, which has an unusually broad substrate range that includes Fe2+, Zn2+, Mn2+, Co2+, Cd2+, Cu2+, Ni2+ and Pb2+. DCT1 mediates active transport that is proton-coupled and depends on the cell membrane potential. It is a 561-amino-acid protein with 12 putative membrane-spanning domains and is ubiquitously expressed, most notably in the proximal duodenum. DCT1 is upregulated by dietary iron deficiency, and may represent a key mediator of intestinal iron absorption. DCT1 is a member of the ‘natural-resistance-associated macrophage protein’ (Nramp) family3,4,5 and thus its properties provide insight into how these proteins confer resistance to pathogens.

Suggested Citation

  • Hiromi Gunshin & Bryan Mackenzie & Urs V. Berger & Yoshimi Gunshin & Michael F. Romero & Walter F. Boron & Stephan Nussberger & John L. Gollan & Matthias A. Hediger, 1997. "Cloning and characterization of a mammalian proton-coupled metal-ion transporter," Nature, Nature, vol. 388(6641), pages 482-488, July.
  • Handle: RePEc:nat:nature:v:388:y:1997:i:6641:d:10.1038_41343
    DOI: 10.1038/41343
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    Cited by:

    1. Gunnar F. Kwakye & Monica M.B. Paoliello & Somshuvra Mukhopadhyay & Aaron B. Bowman & Michael Aschner, 2015. "Manganese-Induced Parkinsonism and Parkinson’s Disease: Shared and Distinguishable Features," IJERPH, MDPI, vol. 12(7), pages 1-22, July.
    2. Layimar Cegarra & Andrea Colins & Ziomara P Gerdtzen & Marco T Nuñez & J Cristian Salgado, 2019. "Mathematical modeling of the relocation of the divalent metal transporter DMT1 in the intestinal iron absorption process," PLOS ONE, Public Library of Science, vol. 14(6), pages 1-26, June.
    3. Fiona Berger & Guillermo M. Gomez & Cecilia P. Sanchez & Britta Posch & Gabrielle Planelles & Farzin Sohraby & Ariane Nunes-Alves & Michael Lanzer, 2023. "pH-dependence of the Plasmodium falciparum chloroquine resistance transporter is linked to the transport cycle," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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