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PMID: 14530973 Published · ppublish English Journal Article Review

SLC11 family of H+-coupled metal-ion transporters NRAMP1 and DMT1.

Pflugers Archiv : European journal of physiology ·Vol. 447 ·No. 5 ·2004-02-00 ·Pages 571-9

Mackenzie B, Hediger MA

Abstract

NRAMP1 (natural resistance-associated macrophage protein-1) and DMT1 (divalent metal-ion transporter-1) make up the SLC11 gene family of metal-ion transporters that are energized by the H(+) electrochemical gradient. Long known to confer resistance to bacterial infection, NRAMP1 functions at the phagolysosomal membrane of macrophages and neutrophils. NRAMP1 most likely contributes to macrophage antimicrobial function by extruding essential metal ions (including Mn(2+)) from the phagolysosome via H(+)/metal-ion cotransport. An alternative hypothesis in the literature proposes that NRAMP1 concentrate Fe(2+) within the phagolysosome by means of H(+)/Fe(2+) antiport, resulting in the generation of toxic free radicals. DMT1 is expressed widely and accepts as substrates a broad range of transition metal ions, among which Fe(2+) is transported with high affinity ( K(0.5) approximately 2 microM). DMT1 accounts both for the intestinal absorption of free Fe(2+) and for transferrin-associated endosomal Fe(2+) transport in erythroid precursors and many other cell types. DMT1 is up-regulated dramatically in the intestine by dietary iron restriction and, despite high serum iron levels, is not appropriately down-regulated in hereditary hemochromatosis.

MeSH Terms
Animals Biological Transport/physiology Cation Transport Proteins/physiology Humans Iron-Binding Proteins/physiology Metals/metabolism Multigene Family/physiology Protons
Chemicals
Cation Transport Proteins Iron-Binding Proteins Metals Protons natural resistance-associated macrophage protein 1 solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Mackenzie Bryan
Membrane Biology Program and Renal Division, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Hediger Matthias A
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Article Info
Journal
Pflugers Archiv : European journal of physiology
Abbr.
Pflugers Arch
ISSN
0031-6768
DOI
10.1007/s00424-003-1141-9
Published
2004-02-00
Epub
2003-00-07
Pages
571-9
Language
English
Region
Germany
NLM ID
0154720
Subset
IM
External Links
PubMed source DOI: 10.1007/s00424-003-1141-9 View journal details
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