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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
Tandy §,
Mark
Williams ¶,
Aime
Leggett ,
Marta
Lopez-Jimenez ,
Markos
Dedes ,
Bala
Ramesh ,
Surjit Kaila
Srai , and
Paul
Sharp ¶**
From the School of Biological Sciences, University of
East Anglia, Norwich, NR4 7TJ, ¶ Institute of Food Research,
Norwich, NR4 7UA, and 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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Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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