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

Pflugers Archiv European Journal of Physiology

Volumn 447, Issue 5, 2004, Pages 571-579

  Mackenzie, Bryan ^a   Hediger, Matthias A ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Anemia; Cadmium; Hepcidin; Hereditary hemochromatosis; Iron transport; Iron responsive element; Reticulocytes; Transferrin cycle

Indexed keywords

CARRIER PROTEIN; FERROUS ION; MANGANESE; MEMBRANE PROTEIN; METAL ION; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 1; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 2; PROTON; SLC11 PROTEIN; TRANSFERRIN; TRANSITION ELEMENT; UNCLASSIFIED DRUG;

ANTIMICROBIAL ACTIVITY; DOWN REGULATION; GENE FUNCTION; HEMOCHROMATOSIS; HUMAN; INTESTINE ABSORPTION; IRON ABSORPTION; IRON BLOOD LEVEL; IRON RESPONSIVE ELEMENT; IRON RESTRICTION; IRON TRANSPORT; LYSOSOME; MACROPHAGE; MEMBRANE BIOLOGY; MULTIGENE FAMILY; NONHUMAN; NUCLEOTIDE SEQUENCE; PATHOPHYSIOLOGY; PHAGOSOME; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INDUCTION; PROTEIN STRUCTURE; PROTON TRANSPORT; REVIEW; STRUCTURE ACTIVITY RELATION; UPREGULATION;

ANIMALS; BIOLOGICAL TRANSPORT; CATION TRANSPORT PROTEINS; HUMANS; IRON-BINDING PROTEINS; METALS; MULTIGENE FAMILY; PROTONS;

EID: 1342281234     PISSN: 00316768     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00424-003-1141-9     Document Type: Review

References (83)

1. Abel L, Sanchez FO, Oberti J, Thuc NV, Hoa LV, Lap VD, Skamene E, Lagrange PH, Schurr E (1998) Susceptibility to leprosy is linked to the human NRAMP1 gene. J Infect Dis 177:133-145
2. Andrews NC (2002) Animal models of iron transport and storage disorders. In: Templeton DM (ed) Molecular and cellular iron transport Marcel Dekker, New York, pp 679-697
3. 1+ transporter of intestinal cells. Am J Physiol 284:C1525-C1530
4. Awomoyi AA, Marchant A, Howson JM, McAdam KP, Blackwell JM, Newport MJ (2002) Interleukin-10, polymorphism in SLC11A1 (formerly NRAMP1), and susceptibility to tuberculosis. J Infect Dis 186:1808-1814
5. Bannon DI, Abounader R, Lees PS, Bressler JP (2003) Effect of DMT1 knockdown on iron, cadmium, and lead uptake in Caco-2 cells. Am J Physiol 284:C44-C50
6. Bassuny WM, Ihara K, Matsuura N, Ahmed S, Kohno H, Kuromaru R, Miyako K, Hara T (2002) Association study of the NRAMP1 gene promoter polymorphism and early-onset type 1 diabetes. Immunogenetics 54:282-285
7. Bellamy R (2003) Susceptibility to mycobacterial infections: the importance of host genetics. Genes Immun 4:4-11
8. Bellamy R, Ruwende C, Corrah T, McAdam KPWJ, Whittle HC, Hill AVS (1998) Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans. New Eng J Med 338:640-644
9. Blackwell JM, Searle S, Mohamed H, White JK (2003) Divalent cation transport and susceptibility to infectious and autoimmune disease: continuation of the Ity/Lsh/Bcg/Nramp1/ Slc11a1 gene story. Immunol Lett 85:197-203
10. Bridle KR, Frazer DM, Wilkins SJ, Dixon JL, Purdie DM, Crawford DH, Subramaniam VN, Powell LW, Anderson GJ, Ram GA (2003) Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet 361:669-673
11. Buchanan GR, Sheehan RG (1981) Malabsorption and defective utilization of iron in three siblings. J Pediatr 98:723-728
12. Canonne-Hergaux F, Gros P (2002) Expression of the iron transporter DMT1 in kidney from normal and anemic mk mice. Kidney Int 62:147-156
13. Canonne-Hergaux F, Gruenheid S, Ponka P, Gros P (1999) Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. Blood 93:4406-4417
14. Canonne-Hergaux F, Fleming MD, Levy JE, Gauthier S, Ralph T, Picard V, Andrews NC, Gros P (2000) The Nramp2/DMT1 iron transporter is induced in the duodenum of microcytic anemia mk mice but is not properly targeted to the intestinal brush border. Blood 96:3964-3970
15. Canonne-Hergaux F, Zhang A-S, Ponka P, Gros P (2001) Characterization of the iron transporter DMT1 (NRAMP2/ DCT1) in red blood cells of normal and anemic mk/mk mice. Blood 98:3823-3830
16. Canonne-Hergaux F, Calafet J, Richer E, Cellier M, Grinstein S, Borregaard N, Gros P (2002) Expression and subcellular localization of NRAMP1 in human neutrophil granules. Blood 100:268-275
17. Casey JL, Hentze MW, Koeller DM, Caughman SW, Rouault TA, Klausner RD, Harford JB (1988) Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation. Science 240:924-928
18. Cellier M, Govoni G, Vidal S, Kwan T, Groulx N, Liu J, Sanchez F, Skamene E, Schurr E, Gros P (1994) Human natural resistance-associated macrophage protein: cDNA cloning, chromosomal mapping, genomic organization, and tissue-specific expression. J Exp Med 180:1741-1752
19. Cellier M, Privé G, Belouchi A, Kwan T, Rodrigues V, Chia W, Gros P (1995) Nramp defines a family of membrane proteins. Proc Natl Acad Sci USA 92:10089-10093
20. Cellier MFM, Bergevin I, Boyer E, Richer E (2001) Polyphyletic origins of bacterial Nramp transporters. Trends Genet 17:365-370
21. +-coupled iron uptake with concomitant uncoupled cation currents. J Biol Chem 274:35089-35094
22. Evans CA, Harbuz MS, Ostenfeld T, Norrish A, Blackwell JM (2001) Nramp1 is expressed in neurons and is associated with behavioural and immune responses to stress. Neurogenetics 3:69-78
23. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R, Jr, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Wolff RK (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399-408
24. Fitness J, Tosh K, Hill AVS (2002) Genetics of susceptibility to leprosy. Genes Immun 3:441-453
25. Fleming MD, Trenor CC, Su MA, Foernzler D, Beier DR, Dietrich WF, Andrews NC (1997) Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet 16:383-386
26. Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD, Andrews NC (1998) Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc Natl Acad Sci USA 95:1148-1153
27. Fleming RE, Migas MC, Zhou X, Jiang J, Britton RS, Brunt EM, Tomatsu S, Waheed A, Bacon BR, Sly WS (1999) Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: increased duodenal expression of the iron transporter DMT1. Proc Natl Acad Sci USA 96:3143-3148
28. Forbes JR, Gros P (2003) Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane. Blood 102:1884-1892
29. Frazer DM, Wilkins SJ, Becker EM, Vulpe CD, McKie AT, Trinder D, Anderson GJ (2002) Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats. Gastroenterology 123:835-844
30. Frehel C, Canonne-Hergaux F, Gros P, De Chastellier C (2002) Effect of Nramp1 on bacterial replication and on maturation of Mycobacterium avium-containing phagosomes in bone marrow-derived mouse macrophages. Cell Microbiol 4:541-556
31. Ganz T (2003) Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 102:783-788
32. Garrick LM, Dolan KG, Romano MA, Garrick MD (1999) Non-transferrin-bound iron uptake in Belgrade and normal rat erythroid cells. J Cell Physiol 178:349-358
33. +/bivalent cation antiporter. Biochem J 354:511-519
34. Govoni G, Gauthier S, Billia F, Iscove NN, Gros P (1997) Cell-specific and inducible Nramp1 gene expression in mouse macrophages in vitro and in vivo. J Leukoc Biol 62:277-286
35. Govoni G, Canonne-Hergaux F, Pfeiffer CG, Marcus SL, Mills SD, Hackam DJ, Grinstein S, Malo D, Finlay BB, Gros P (1999) Functional expression of Nramp1 in vitro after transfection into the murine macrophage line RAW264.7. Infect Immun 67:2225-2232
36. Gruenheid S, Cellier M, Vidal S, Gros P (1995) Identification and characterization of a second mouse Nramp gene. Genomics 25:514-525
37. Gruenheid S, Pinner E, Desjardins M, Gros P (1997) Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome. J Exp Med 185:717-730
38. Gruenheid S, Canonne-Hergaux F, Gauthier S, Hackam DJ, Grinstein S, Gros P (1999) The iron transport protein NRAMP2 is an integral membrane glycoprotein that colocalizes with transferrin in recycling endosomes. J Exp Med 189:831-841
39. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA (1997) Cloning and characterization of a proton-coupled mammalian metal-ion transporter. Nature 388:482-488
40. Hackam DJ, Rotstein OD, Zhang W, Gruenheid S, Gros P, Grinstein S (1998) Host resistance to intracellular infection: mutation of natural resistance-associated macrophage protein 1 (Nramp1) impairs phagosomal acidification. J Exp Med 188:351-364
41. Harrison SA, Bacon BR (2003) Hereditary hemochromatosis: update for 2003. J Hepatol 38 (Suppl 1):S14-S23
42. Hartman KR, Barker JA (1996) Microcytic anemia with iron malabsorption: an inherited disorder of iron metabolism. Am J Hematol 51:269-275
43. Hentze MW, Kühn LC (1996) Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. Proc Natl Acad Sci USA 93:8175-8182
44. Hofmeister A, Neibergs HL, Pokorny RM, Galandiuk S (1997) The natural resistance-associated macrophage protein gene is associated with Crohn's disease. Surgery 122:173-178
45. Hubert N, Hentze MW (2002) Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function. Proc Natl Acad Sci USA 99:12345-12350
46. Jabado N, Jankowski A, Dougaparsad S, Picard V, Grinstein S, Gros P (2000) Natural resistance to intracellular infections: natural resistance-associated macrophage protein 1 (Nramp1) functions as a pH-dependent manganese transporter at the phagosomal membrane. J Exp Med 192:1237-1248
47. Jabado N, Canonne-Hergaux F, Gruenheid S, Picard V, Gros P (2002) Iron transporter Nramp2/DMT-1 is associated with the membrane of phagosomes in macrophages and Sertoli cells. Blood 100:2617-2622
48. Kishi F (1994) Isolation and characterization of human Nramp cDNA. Biochem Biophys Res Commun 204:1074-1080
49. Kishi F, Tabuchi M (1998) Human natural resistance-associated macrophage protein 2: gene cloning and protein identification. Biochem Biophys Res Commun 251:775-783
50. Asp169. J Leukoc Biol 66:113-119
51. Gly169-transfected RAW264. 7 macrophage cell line. J Leukoc Biol 69:43-49
52. Lam-Yuk-Tseung S, Govoni G, Gros P (2003) Iron transport by NRAMP2/DMT1: pH regulation of transport by two histidines in transmembrane domain 6. Blood 101:3699-3707
53. Lee PL, Gelbart T, West C, Halloran C, Beutler E (1998) The human Nramp2 gene: characterization of the gene structure, alternative splicing, promoter region and polymorphisms. Blood Cells Mol Dis 24:199-215
54. Mackenzie B, Ujwal ML, Chang M-H, Romero MF, Hediger MA (2003) Resolving the mechanisms of the iron transporter DCT1 from its kinetic properties and the impact of mutating two critical histidyl residues within transmembrane regions (abstract). FASEB J 17:A911
55. McEwan GTA, Daniel H, Fett C, Burgess MN, Lucas ML (1988) The effect of Escherichia coli STa enterotoxin and other secretagogues on mucosal surface pH of rat small intestine in vivo. Proc R Soc Lond B 234:219-237
56. Muckenthaler M, Roy CN, Custodio ÁO, Miñana B, deGraaf J, Montross LK, Andrews NC, Hentze MW (2003) Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis. Nat Genet 34:102-107
57. Nelson N, Harvey WR (1999) Vacuolar and plasma membrane proton-adenosinetriphosphatases. Physiol Rev 79:361-385
58. Ouchi K, Suzuki Y, Shirakawa T, Kishi F (2003) Polymorphism of SLC11A1 (formerly NRAMP1) gene confers susceptibility to Kawasaki disease. J Infect Dis 187:326-329
59. Page RDM (1996) TreeView: an application to display phylogenetic trees on personal computers. Comput Appl Biosci 12:357-358
60. Picard V, Govoni G, Jabado N, Gros P (2000) Nramp 2 (DCT1/DMT1) expressed at the plasma membrane transports iron and other divalent cations into a calcein-accessible cytoplasmic pool. J Biol Chem 275:35738-35745
61. Pietrangelo A (2002) Physiology of iron transport and the hemochromatosis gene. Am J Physiol 282:G403-G414
62. Roig EA, Richer E, Canonne-Hergaux F, Gros P, Cellier MF (2002) Regulation of NRAMP1 gene expression by 1-α,25-dihydroxy-vitamin D3 in HL-60 phagocytes. J Leukoc Biol 71:890-904
63. Rolfs A, Bonkovsky HL, Kohlroser JG, McNeal K, Sharma A, Berger UV, Hediger MA (2002) Intestinal expression of genes involved in iron absorption in humans. Am J Physiol 282:G598-G607
64. Sacher A, Cohen A, Nelson N (2001) Properties of the mammalian and yeast metal-ion transporters DCT1 and Smf1p expressed in Xenopus laevis oocytes. J Exp Biol 204:1053-1061
65. Searle S, Bright NA, Roach TIA, Atkinson PGP, Barton CH, Meloen RH, Blackwell JM (1998) Localisation of Nramp1 in macrophages: modulation with activation and infection. J Cell Sci 111:2855-2866
66. Skamene E, Schurr E, Gros P (1998) Infection genomics: Nramp1 as a major determinant of natural resistance to intracellular infections. Annu Rev Med 49:275-287
67. Soborg A, Andersen AB, Madsen HO, Kok-Jensen A, Skinhoj P, Garred P (2002) Natural resistance-associated macrophage protein 1 polymorphisms are associated with microscopy-positive tuberculosis. J Infect Dis 186:517-521
68. Stuart KA, Anderson GJ, Frazer DM, Powell LW, McCullen M, Fletcher LM, Crawford DH (2003) Duodenal expression of iron transport molecules in untreated haemochromatosis subjects. Gut 52:953-959
69. Su MA, Trenor CC, Fleming JC, Fleming MD, Andrews NC (1998) The G185R mutation disrupts function of the iron transporter Nramp2. Blood 92:2157-2163
70. Supek F, Supekova L, Nelson H, Nelson N (1996) A yeast manganese transporter related to the macrophage protein involved in conferring resistance to mycobacteria. Proc Natl Acad Sci USA 93:5105-5110
71. Tabuchi M, Yoshimori T, Yamaguchi K, Yoshida T, Kishi F (2000) Human NRAMP2/DMT1, which mediates iron transport across endosomal membranes, is localized to late endosomes and lysosomes in HEp-2 cells. J Biol Chem 275:22220-22228
72. Tabuchi M, Tanaka N, Nishida-Kitayama J, Ohno H, Kishi F (2002) Alternative splicing regulates the subcellular localization of divalent metal transporter 1 isoforms. Mol Biol Cell 13:4371-4387
73. Tandy S, Williams M, Leggett A, Lopez-Jimenez M, Dedes M, Ramesh B, Srai SK, Sharp P (2000) Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells. J Biol Chem 275:1023-1029
74. Tatusova TA, Madden TL (1999) BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequences. FEMS Microbiol Lett 174:247-250
75. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673-4680
76. Touret N, Furuya W, Forbes J, Gros P, Grinstein S (2003) Dynamic traffic through the recycling compartment couples the metal transporter Nramp2 (DMT1) with the transferrin receptor. J Biol Chem 278:25548-25557
77. Vidal SM, Malo D, Vogan K, Skamene E, Gros P (1993) Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell 73:469-485
78. Vidal S, Belouchi AM, Cellier M, Beatty B, Gros P (1995) Cloning and characterization of a second human NRAMP gene on chromosome 12q13. Mammal Genome 6:224-230
79. Vidal SM, Pinner E, Lepage P, Gauthier S, Gros P (1996) Natural resistance to intracellular infections: Nramp1 encodes a membrane phosphoglycoprotein absent in macrophages from susceptible (Nramp1 D169) mouse strains. J Immunol 157:3559-3568
80. Waheed A, Parkkila S, Saarnio J, Fleming RE, Zhou XY, Tomatsu S, Britton RS, Bacon BR, Sly WS (1999) Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum. Proc Natl Acad Sci USA 96:1579-1584
81. Zhong W, Lafuse WP, Zwilling BS (2001) Infection with Mycobacterium avium differentially regulates the expression of iron transport protein mRNA in murine peritoneal macrophages. Infect Immun 69:6618-6624
82. Zoller H, Koch RO, Theurl I, Obrist P, Pietrangelo A, Montosi G, Haile DJ, Vogel W, Weiss G (2001) Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload. Gastroenterology 120:1412-1419
83. Zwilling BS, Kuhn DE, Wikoff L, Brown D, Lafuse W (1999) Role of iron in Nramp1-mediated inhibition of mycobacterial growth. Infect Immun 67:1386-1392