Cloning and characterization of a mammalian proton-coupled metal-ion transporter
Hiromi Gunshin (),
Bryan Mackenzie,
Urs V. Berger,
Yoshimi Gunshin,
Michael F. Romero,
Walter F. Boron,
Stephan Nussberger,
John L. Gollan and
Matthias A. Hediger ()
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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
Nature, 1997, vol. 388, issue 6641, 482-488
Abstract:
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.
Date: 1997
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DOI: 10.1038/41343
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