Divalent metal transporter 1

Hematology

Volumn 10, Issue 4, 2005, Pages 339-345

  Mims, Martha P ^a   Prchal, Josef T ^b  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b MICHAEL E DEBAKEY VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Alternative splicing; Iron metabolism; Microcytic anemia; Nramp2; Tissue specific mRNA processing

Indexed keywords

IRON; MESSENGER RNA; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 2;

ALTERNATIVE RNA SPLICING; CANCER CELL; DUODENUM; GENE MUTATION; GENE STRUCTURE; GENETIC VARIABILITY; HUMAN; INTESTINE CELL; IRON METABOLISM; IRON TRANSPORT; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVIEW; SIGNAL TRANSDUCTION;

ALTERNATIVE SPLICING; ANEMIA, IRON-DEFICIENCY; ANIMALS; CATION TRANSPORT PROTEINS; EVOLUTION, MOLECULAR; GENE EXPRESSION REGULATION; HUMANS; ION TRANSPORT; IRON; IRON OVERLOAD; IRON-BINDING PROTEINS; MICE; MUTATION; RATS;

EID: 29144450958     PISSN: 10245332     EISSN: 16078454     Source Type: Journal    
DOI: 10.1080/10245330500093419     Document Type: Review

References (61)

1. Fox BG. Catalysis by non-heme iron-containing enzymes. In: Sinnott M, editor. Comprehensive biological catalysis. Vol. 3. London: Academic Press; 1997. p 266-348.
2. McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, Barrow D, Miret S, Bomford A, Peters TJ, Farzaneh F, Hediger MA, Hentze MW, Simpson RJ. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 2000;5:299-309.
3. Conrad ME, Umbreit JN. Iron absorption and transport - an update. Am J Hematol 2000;64:287-298.
4. Simovich M, Hainsworth LN, Fields PA, Umbreit JN, Conrad ME. Localization of the iron transport proteins Mobilferrin and DMT-1 in the duodenum: The surprising role of mucin. Am J Hematol 2003;74:32-45.
5. Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, Libina N, Gitschier J, Anderson GJ. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet 1999;21:195-199.
6. Trenor CC, Campagna DR, Sellers VM, Andrews NC, Fleming MD. The molecular defect in hypotransferrinemic mice. Blood 2000;96:1113-1118.
7. Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD, Andrews NC. Nramp2 is mutated in the anemic Belgrade (b) rat: Evidence of a role for Nramp2 in endosomal iron transport. Proc Natl Acad Sci USA 1998;95:1148-1153.
8. Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 2001;276:7806-7810.
9. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 2003;101:2461-2463.
10. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004;306:2090-2093.
11. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 1997;388:482-488.
12. Gruenheid S, Cellier M, Vidal S, Gros P. Identification and characterization of a second mouse Nramp gene. Genomics 1995;25:514-525.
13. Lee P, Gelbart T, West C, Halloran C, Beutler E. The human Nramp2 gene: Characterization of the gene structure, alternative splicing, promoter region and polymorphisms. Blood Cells Mol Dis 1998;24:199-215.
14. Picard V, Govoni G, Jabado N, Gros P. Nramp 2 (DCT1/DMT1) expressed at the plasma membrane transports iron and other divalent cations into a calcein-accessible cytoplasmic pool. J Biol Chem 2000;275:35738-35745.
15. Fleming MD, Treno 3rd, CC, Su MA, Foernzler D, Beier DR, Dietrich WF, Andrews NC. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet 1997;16:383-386.
16. Su M, Trenor CC, Fleming JC, Fleming MD, Andrews NC. The G185R mutation disrupts function of the iron transporter Nramp2. Blood 1998;92:2157-2163.
17. 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 USA 1995;92:10089-10093.
18. Zoller H, Theurl I, Koch R, Kaser A, Weiss G. Mechanisms of iron mediated regulation of the duodenal iron transporters divalent metal transporter 1 and ferroportin 1. Blood Cells Mol Dis 2002;29:488-497.
19. Tandy S, Williams M, Leggett A, Lopez-Jimenez M, Dedes M, Ramesh B, Srai SK, Sharp P. Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells. J Biol Chem 2000;275:1023-1029.
20. Garrick MD, Dolan KG, Ghio A, Horbinsk C, Higgins D, Porubcin M, Moore EG, Hainsworth LN, Umbreit JN, Conrad ME, Feng L, Lis A, Roth JA, Singleton S, Garrick LM. DMT1: A mammalian transporter for multiple metals. Biometals 2003;16:41-54.
21. Bannon DI, Portnoy ME, Olivi L, Lees PSJ, Culotta VC, Bressler JP. Uptake of lead and iron by divalent metal trasporter 1 in yeast and mammalian cells. Biochem Biophys Res Comm 2002;295:978-984.
22. Forbes JR, Gros P. Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane. Blood 2003;102:1884-1892.
23. Conrad ME, Umbreit JN, Moore EG, Hainsworth LN, Porubcin M, Simovich MJ, Nakada MT, Dolan K, Garrick MD. Separate pathways for cellular uptake of ferric and ferrous iron. Am J Physiol Gastrointest Liver Physiol 2000;279:G767-G774.
24. Edwards JA, Garrick LM, Hoke JE. Defective iron uptake and globin synthesis by erythroid cells in the anemia of the belgrade laboratory rat. Blood 1978;51:347-357.
25. Garrick M, Scott D, Walpole S, Finkelstein E, Whitbred J, Chopra S, Trivikram L, Mayes D, Rhodes D, Cabbagestalk K, Oklu R, Sadiq A, Mascia B, Hoke J, Garrick L. Iron supplementation moderates but does not cure the Belgrade anemia. Biometals 1997;10:65-76.
26. Garrick MD, Gniecko L, Liu Y, Eckert B, Grasso JA, Garrick LM. Elevated endosomal pH in Belgrade rat reticulocytes. J Cell Biol 1990;111:82a.
27. Garrick MD, Gniecko L, Liu Y, Cohan D, Eckert BS, Grasso JA, et al. Defective endosomal acidification in Belgrade rat reticulocytes. Blood 1990;768b.
28. Lam-Yuk-Tseung S, Govoni G, Forbes J, Gros P. Iron transport by Nramp2/DMT1: pH regulation of transport by 2 histidines in transmembrane domain 6. Blood 2003;101:3699-3707.
29. Xu H, Jin J, DeFelice LJ, Andrews NC, Clapham DE. Spontaneous, recurrent mutation in divalent metal transporter-1 exposes a calcium entry pathway. PLoS Biol 2004;2:E50.
30. Canonne-Hergaux S, Gruenheid S, Ponka P, Gros P. Cellular and subcellular localizaton of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. Blood 1999;93:4406-4417.
31. Gruenheid S, Canonne-Hergaux F, Gauthier S, Hackam DJ, Grinstein S, Gros P. The iron transport protein NRAMP2 is an integral membrane glycoprotein that colocalizes with transferrin in recycling endosomes. J Exp Med 1999;189:831-841.
32. Canonne-Hergaux S, Zhang AS, Ponka P, Gros P. Characterization of the iron transporter DMT1(NRMAP2/DCT1) in red blood cells of normal and anemic mk/mk mice. Blood 2001;98:3823-3830.
33. Ferguson CJ, Wareing M, Ward DT, Green R, Smith CP, Riccardi D. Cellular localization of divalent metal transporter DMT-1 in rat kidney. Am J Physiol Renal Physiol 2001;280:F803-F814.
34. Canonne-Hergaux F, Gros P. Expression of the iron transporter DMT1 in kidney from normal and anemic mk mice. Kidney Int 2002;62:147-156.
35. Ferguson CJ, Wareing M, Delannoy M, Fenton R, McLarnon SJ, Ashton N, Cox AG, McMahon RF, Garrick LM, Green R, Smith CP, Riccardi D. Iron handling and gene expression of the divalent metal transporter, DMT1, in the kidney of the anemic Belgrade (b) rat. Kidney Int 2003;64:1755-1764.
36. Moos T, Morgan EH. The significance of the mutated divalent metal transporter (DMT1) on iron transport into the Belgrade rat brain. J Neurochem 2004;88:233-245.
37. Wang XS, Ong WY, Connor JR. A light and electron microscopic study of the iron transporter protein DMT-1 in the monkey cerebral neocortex and hippocampus. J Neurocytol 2001;30:353-360.
38. Moos T, Morgan EH. The metabolism of neuronal iron and its pathogenic role in neurological disease: Review. Ann NY Acad Sci 2004;1012:14-26.
39. Tchernitchko D, Bourgeois M, Martin M, Beaumont C. Expression of the two mRNA isoforms of the iron transporter Nramp2/DMT1 in mice and function of the iron responsive element. Biochem J 2002;363:449-455.
40. Hubert N, Hentze MW. Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: Implications for regulation and cellular function. Proc Natl Acad Sci USA 2002;99:12345-12350.
41. Mims MP, Guan Y, Prchal JT. DMT1: Tissue specific expression and alternative splicing. Blood 2004;104:A3210.
42. Tabuchi M, Tanaka N, Nishida-Kitayama J, Ohno H, Kishi F. Alternative splicing regulates the subcellular localization of divalent metal transporter 1 isoforms. Mol Biol Cell 2002;13:4371-4387.
43. Touret N, Martin-Orozco N, Paroutis P, Furuya W, Lam-Yuk-Tseung S, Forbes J, Gros P, Grinstein S. Molecular and cellular mechanisms underlying iron transport deficiency in microcytic anemia. Blood 2004;104:1526-1533.
44. Gunshin H, Allerson CR, Polycarpou-Schwarz M, Rofts A, Rogers JT, Kishi F, Hentze MW, Rouault TA, Andrews NC, Hediger MA. Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett 2001;509:309-316.
45. Dupic F, Fruchon S, Bensaid M, Loreal O, Brissot P, Borot N, Roth MP, Coppin H. Duodenal mRNA expression of iron related genes in response to iron loading and iron deficiency in four strains of mice. Gut 2002;51:648-653.
46. LaVaute T, Smith S, Cooperman S, Iwai K, Land W, Meyron-Holtz E, Drake SK, Miller G, Abu-Asab M, Tsokos M, Switzer 3rd, R, Grinberg A, Love P, Tresser N, Rouault TA. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet 2000;27:209-214.
47. Yeh KY, Yeh M, Watkins JA, Rodriguez-Paris J, Glass J. Dietary iron induces rapid changes in rat intestinal divalent metal transporter expression. Am J Physiol Gastrointest Liver Physiol 2000;279:G1070-G1079.
48. Chen H, Su T, Attieh ZK, Fox TC, McKie AT, Anderson GJ, Vulpe CD. Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency. Blood 2003;102:1893-1899.
49. Byrnes V, Barrett S, Ryan E, Kelleher T, O'Keane C, Coughlan B, Crowe J. Increased duodenal DMT-1 expression and unchanged HFE mRNA levels in HFE-associated hereditary hemochromatosis and iron deficiency. Blood Cells Mol Dis 2002;29:251-260.
50. Canonne-Hergaux F, Levy JE, Fleming MD, Montross LK, Andrews NC, Gros P. Expression of the DMT1 (NRAMP2/DCT1) iron transporter in mice with genetic iron overload disorders. Blood 2001;97:1138-1140.
51. Fleming RE, Migas MC, Zhou X, Jiang J, Britton RS, Brunt EM, Tomatsu S, Waheed A, Bacon BR, Sly WS. Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: Increased duodenal expression of the iron transporter DMT1. Proc Natl Acad Sci USA. 1999;96:3143-3148.
52. Muckenthaler M, Roy CN, Custodio AO, Minana B, deGraaf J, Montross LK, Andrews NC, Hentze MW. Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis. Nat Genet 2003;34:102-107.
53. Frazer DM, Wilkins SJ, Becker EM, Vulpe CD, McKie AT, Trinder D, Anderson GJ. Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats. Gastroenterology 2002;123:835-845.
54. Yamaji S, Sharp P, Ramesh B, Srai SK. Inhibition of iron transport across human intestinal epithelial cells by hepcidin. Blood 2004;104:2178-2180.
55. Chua AC, Olynyk JK, Leedman PJ, Trinder D. Nontransferrin-bound iron uptake by hepatocytes is increased in the Hfe knockout mouse model of hereditary hemochromatosis. Blood 2004;104:1519-1525.
56. Ludwiczek S, Aigner E, Theurl I, Weiss G. Cytokine-mediated regulation of iron transport in human monocytic cells. Blood 2003;101:4148-4154.
57. Zoller H, Decristoforo C, Weiss G. Erythroid 5-aminolevulinate synthase, ferrochelatase and DMT1 expression in erythroid progenitors: Differential pathways for erythropoietin and iron dependent regulation. Br J Haematol 2002;118:619-626.
58. Donovan A, Brownlie A, Dorschner MO, Zhou Y, Pratt SJ, Paw BH, Phillips RB, Thisse C, Thisse B, Zon LI. The zebrafish mutant gene chardonnay (cdy) encodes divalent metal transporter 1 (DMT1). Blood 2002;100:4655-4659.
59. Priwitzerova M, Pospisilova D, Prchal JT, Indrak K, Hlobilkova A, Mihal V, Ponka P, Divoky V. Severe hypochromic microcytic anemia caused by a congenital defect of the iron transport pathway in erythroid cells. Blood 2004;103:3991-3992.
60. Mims MP, Guan Y, Pospisilova D, Priwitzerova M, Indrak K, Ponka P, Divoky V, Prchal JT. Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload. Blood 2005;105:1337-1342.
61. Gunshin H, Fujiwara Y, Custodio AO, DiRenzo C, Robine S, Andrews NC. Iron metabolism in the mice with targeted mutations of the DMT1 gene. Blood 2004;104, Abstract 50.