Molecular insights into mechanisms of iron transport

Current Opinion in Hematology

Volumn 6, Issue 2, 1999, Pages 61-64

  Andrews, Nancy C ^a   Fleming, Mark D ^a   Levy, Joanne E ^a  

^a BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL PROTEIN; IRON;

GENE FUNCTION; GENE MUTATION; GENE STRUCTURE; HEMOCHROMATOSIS; HOMEOSTASIS; HUMAN; IRON OVERLOAD; IRON TRANSPORT; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANIMALS; BIOLOGICAL TRANSPORT; CARRIER PROTEINS; HEMOCHROMATOSIS; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; IRON; IRON OVERLOAD; MAMMALS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032775091     PISSN: 10656251     EISSN: None     Source Type: Journal    
DOI: 10.1097/00062752-199903000-00001     Document Type: Review

References (27)

1. Fleming MD, Trenor CCI, Su MA, Foernzler D, Beier DR, Dietrich WF, Andrews NC: Microcytic anemia mice have a mutation in Nramp2, a candidate iron transporter. Nat Genet 1997, 16:383-386.
2. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, et al.: Cloning and characterization of a mammalian proton-coupled metalion transporter. Nature 1997, 388;482-488.
3. Su MA, Trenor CC, Fleming JC, Fleming MD, Andrews NC: The G185R mutation disrupts function of iron transporter Nramp2. Blood 1998, 92:2157-2163. Expression studies indicate that the G185R mutation is highly deleterious. This paper shows that DMT1 localizes to the plasma membrane and to transferrin cycle endosomes; the G185R mutation disrupts function without altering localization.
4. Grunheid S, Cellier M, Vidal S, Gros P: Identification and characterization of a second mouse Nramp gene. Genomics 1995, 25:514-525.
5. Vidal SM, Malo D, Vogan K, Skamene E, Gros P: Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell 1993, 73:469-485.
6. Fleming MD, Romano MA, Garrick LM, Garrick MD, Andrews NC: Anemia of the Belgrade rat is caused by a mutation in iron transporter protein Nramp2. Proc Natl Acad Sci U S A 1998, 95:1148-1153. Strikingly, b rats have the same G185R mutation in DMT1 as that seen in mk mice. This indicates that DMT1 is important for iron transport in transferrin cycle endosomes.
7. Cellier M, Prive G, Belouchi A, Kwan T, Rodrigues V, Chia W, Gros P: Nramp defines a family of membrane proteins. Proc Natl Acad Sci U S A 1995, 92:10089-10093.
8. Supek F, Supekova L, Nelson H, Nelson N: A yeast manganese transporter related to the macrophage protein involved in conferring resistance to mycobacteria. Proc Natl Acad Sci U S A 1996, 93:5105-5110.
9. Pinner E, Gruenheid S, Raymond M, Gros P: Functional complementation of the yeast divalent cation transporter family SMF by NRAMP2, a member of the mammalian natural resistance-associated macrophage protein family. J Biol Chem 1997, 272:28933-28938.
10. Atkinson PG, Barton CH: Ectopic expression of Nramp1 in COS-1 cells modulates iron accumulation. FEBS Lett 1998, 425:239-242.
11. Rodrigues V, Cheah PY, Ray K, Chia W: Malvolio, the Drosophila homologue of mouse NRAMP-1 (Bcg), is expressed in macrophages and in the nervous system and is required for normal taste behavior. EMBO J 1995, 14:3007-3020.
12. Orgad S, Nelson H, Segal D, Nelson N: Metal ions suppress the abnormal taste behavior of the Drosophila mutant malvolio. J Exp Biol 1998, 201:115-120.
13. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, et al.: A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 1996, 13:399-408.
14. Feder JN, Tsuchihashi Z, Irrinki A, Lee VK, Mapa FA, Morikang E, et al.: The hemochromatosis founder mutation in HLA-H disrupts beta2-microglobulin interaction and cell surface expression. J Biol Chem 1997, 272:14025-14028.
15. Waheed A, Parkkila S, Zhou XY, Tomatsu S, Tsuchihashi Z, Feder JN, et al.: Hereditary hemochromatosis: effects of C282Y and H63D mutations on association with beta2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells. Proc Natl Acad Sci U S A 1997, 94:12384-12389.
16. Parkkila S, Waheed A, Britton RS, Bacon BR, Zhou XY, Tomatsu S, et al.: Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis. Proc Natl Acad Sci U S A 1997, 94:13198-13202.
17. Feder JN, Penny DM, Irrinki A, Lee VK, Lebron JA, Watson N, et al.: The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. Proc Natl Acad Sci U S A 1998, 95:1472-1477.
18. Lebron JA, Bennett MJ, Vaughn DE, Chirino AJ, Snow PM, Mintier GA, et al.: Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 1998, 93:111-123. The crystal structure of HFE is reported in this paper. It differs from that of other HLA class I-like molecules in that it does not bind a small peptide. The interaction between HFE and TfR is explored, and the implications of the interaction are discussed.
19. Zhou XY, Tomatsu S, Fleming RE, Parkkila S, Waheed A, Jiang J, et al.: HFE gene knockout produces mouse model of hereditary hemochromatosis. Proc Natl Acad Sci U S A 1998, 95:2492-2497. This is the first report of mice that lack HFE protein. These mice develop severe iron overload early in life.
20. de Sousa M, Reimao R, Lacerda R, Hugo P, Kaufmann SHE, Porto G: Iron overload in beta2-microglobulin deficient mice. Immunol Lett 1994, 39:105-111.
21. Santos M, Schilham MW, Rademakers LHPM, Marx JJM, deSousa M, Clevers M: Defective iron homeostasis in beta2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man. J Exp Med 1996, 184:1975-1985.
22. Pietrangelo A: Hemochromatosis 1998: is one gene enough? J Hepatol 1998, 29:502-509.
23. Gordeuk V, Mukiibi J, Hasstedt SJ, Samowitz W, Edwards CQ, West G, et al.: Iron overload in Africa. Interaction between a gene and dietary iron content. N Engl J Med 1992, 326:95-100.
24. Moyo VM, Gangaidzo IT, Gomo ZA, Khumalo H, Saungweme T, Kiire CF, et al.: Traditional beer consumption and the iron status of spouse pairs from a rural community in Zimbabwe. Blood 1997, 89:2159-2166.
25. Gordeuk V, McLaren C, Looker A, Hasselblad V, Brittenham G: Distribution of transferrin saturations in the African-American population. Blood 1998, 91:2175-2179. Little is known about iron overload in African Americans. This paper begins to explore this important subject.
26. Monaghan KG, Rybicki BA, Shurafa M, Feldman GL: Mutation analysis of the HFE gene associated with hereditary hemochromatosis in African Americans. Am J Hematol 1998, 58:213-217.
27. Camaschella C, Roetto A, Cicilano M, Pasquero P, Bosio S, Gubetta L, et al.: Juvenile and adult hemochromatosis are distinct genetic disorders. Eur J Hum Genet 1997, 5:371-375. This important paper presents clear evidence of a new, more severe form of hemochromatosis. The biological implications are striking - it seems that juvenile hemochromatosis results from a defect in an as yet unknown protein that must operate in the HFE regulatory pathway.