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J Biol Chem, Vol. 275, Issue 2, 1023-1029, January 14, 2000

Nramp2 Expression Is Associated with pH-dependent Iron Uptake across the Apical Membrane of Human Intestinal Caco-2 Cells*

Sarah TandyDagger §, Mark WilliamsDagger , Aime LeggettDagger , Marta Lopez-JimenezDagger , Markos DedesDagger , Bala Rameshpar , Surjit Kaila Sraipar , and Paul SharpDagger **

From the Dagger  School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ,  Institute of Food Research, Norwich, NR4 7UA, and par  Department of Biochemistry and Molecular Biology, Royal Free Hospital and University College Medical School, London NW3 2PF, United Kingdom

The absorption of dietary non-heme iron by intestinal enterocytes is crucial to the maintenance of body iron homeostasis. This process must be tightly regulated since there are no distinct mechanisms for the excretion of excess iron from the body. An insight into the cellular mechanisms has recently been provided by expression cloning of a divalent cation transporter (DCT1) from rat duodenum and positional cloning of its human homologue, Nramp2. Here we demonstrate that Nramp2 is expressed in the apical membrane of the human intestinal epithelial cell line, Caco 2 TC7, and is associated with functional iron transport in these cells with a substrate preference for iron over other divalent cations. Iron transport occurs by a proton-dependent mechanism, exhibiting a concurrent intracellular acidification. Taken together, these data suggest that the expression of the Nramp2 transporter in human enterocytes may play an important role in intestinal iron absorption.


* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Supported by a Biotechnology and Biological Sciences Research Council Research Committee Studentship.

** To whom correspondence should be addressed. Tel.: 44 1603 592244; Fax: 44 1603 592250; E-mail: p.a.sharp@uea.ac.uk.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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