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, Matthiaa A. Hediger

Research output: Contribution to journalArticlepeer-review

2465 Scopus citations

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 haemochromatosis, disorders of metal-ion deficiency, and certain neurodegenerative diseases. 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, DGT1, 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) family and thus its properties provide insight into how these proteins confer resistance to pathogens.

Original languageEnglish (US)
Pages (from-to)482-488
Number of pages7
JournalNature
Volume388
Issue number6641
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Cloning and characterization of a mammalian proton-coupled metal-ion transporter'. Together they form a unique fingerprint.

Cite this