Hereditary hemochromatosis and transferrin receptor 2

Biochimica et Biophysica Acta - General Subjects

Volumn 1820, Issue 3, 2012, Pages 256-263

  Chen, Juxing ^a   Enns, Caroline A ^a  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

BMP; Ferroportin; Hemojuvelin; Hepcidin; HFE; TfR2

Indexed keywords

CD71 ANTIGEN; ERYTHROPOIETIN; ERYTHROPOIETIN RECEPTOR; FERRITIN; FERROPORTIN; HEMOGLOBIN; HEMOJUVELIN; HEPCIDIN; HFE PROTEIN; MATRIPTASE; MATRIPTASE 2; MESSENGER RNA; TRANSFERRIN; TRANSFERRIN RECEPTOR 2; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; BIOACCUMULATION; ERYTHROPOIESIS; GENE; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE MUTATION; HEMOCHROMATOSIS; HEMOGLOBIN SYNTHESIS; HEPCIDIN GENE; HFE GENE; HUMAN; INTERNALIZATION; INTRACELLULAR SIGNALING; IRON BALANCE; IRON DEFICIENCY ANEMIA; IRON OVERLOAD; IRON TRANSPORT; LIVER FUNCTION; LIVER METABOLISM; MOLECULAR MECHANICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; RECEPTOR GENE; REVIEW; TRANSFERRIN RECEPTOR 1 GENE; TRANSFERRIN RECEPTOR 2 GENE;

ANEMIA, IRON-DEFICIENCY; ANTIMICROBIAL CATIONIC PEPTIDES; CATION TRANSPORT PROTEINS; ERYTHROPOIESIS; HEMOCHROMATOSIS; HUMANS; INTESTINAL MUCOSA; INTESTINES; ION TRANSPORT; IRON; LIVER; MACROPHAGES; RECEPTORS, TRANSFERRIN;

EID: 84857371872     PISSN: 03044165     EISSN: 18728006     Source Type: Journal    
DOI: 10.1016/j.bbagen.2011.07.015     Document Type: Review

References (139)

1. C. Finch Regulators of iron balance in humans Blood 84 1994 1697 1702 (Pubitemid 24286117)
2. M.W. Gavin, D.M. McCarthy, and P.J. Garry Evidence that iron stores regulate iron absorption-a setpoint theory Am. J. Clin. Nutr. 59 1994 1376 1380 (Pubitemid 24165893)
3. J.R. Hunt, and Z.K. Roughead Adaptation of iron absorption in men consuming diets with high or low iron bioavailability Am. J. Clin. Nutr. 71 2000 94 102 (Pubitemid 30033590)
4. M.H. Nathanson, A. Muir, and G.D. McLaren Iron absorption in normal and iron-deficient beagle dogs: mucosal iron kinetics Am. J. Physiol. 249 1985 G439 G448 (Pubitemid 16201170)
5. M.H. Sayers, G. English, and C. Finch Capacity of the store-regulator in maintaining iron balance Am. J. Hematol. 47 1994 194 197 (Pubitemid 24333447)
6. B.S. Skikne, and J.D. Cook Effect of enhanced erythropoiesis on iron absorption J. Lab. Clin. Med. 120 1992 746 751
7. R.E. Fleming, and W.S. Sly Hepcidin: a putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease Proc. Natl. Acad. Sci. U.S.A. 98 2001 8160 8162 (Pubitemid 32678004)
8. A. Krause, S. Neitz, H.J. Magert, A. Schulz, W.G. Forssmann, P. Schulz-Knappe, and K. Adermann LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity FEBS Lett. 480 2000 147 150
9. G. Nicolas, M. Bennoun, I. Devaux, C. Beaumont, B. Grandchamp, A. Kahn, and S. Vaulont Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice Proc. Natl. Acad. Sci. U.S.A. 98 2001 8780 8785 (Pubitemid 32678104)
10. C. Pigeon, G. Ilyin, B. Courselaud, P. Leroyer, B. Turlin, P. Brissot, and O. Loreal A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload J. Biol. Chem. 276 2001 7811 7819
11. C.H. Park, E.V. Valore, A.J. Waring, and T. Ganz Hepcidin, a urinary antimicrobial peptide synthesized in the liver J. Biol. Chem. 276 2001 7806 7810
12. D.A. Weinstein, C.N. Roy, M.D. Fleming, M.F. Loda, J.I. Wolfsdorf, and N.C. Andrews Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease Blood 100 2002 3776 3781 (Pubitemid 35303951)
13. L. Viatte, G. Nicolas, D.Q. Lou, M. Bennoun, J.C. Lesbordes-Brion, F. Canonne-Hergaux, K. Schonig, H. Bujard, A. Kahn, N.C. Andrews, and S. Vaulont Chronic hepcidin induction causes hyposideremia and alters the pattern of cellular iron accumulation in hemochromatotic mice Blood 107 2006 2952 2958
14. C.N. Roy, H.H. Mak, I. Akpan, G. Losyev, D. Zurakowski, and N.C. Andrews Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation Blood 109 2007 4038 4044 (Pubitemid 46641759)
15. S. Rivera, L. Liu, E. Nemeth, V. Gabayan, O.E. Sorensen, and T. Ganz Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia Blood 105 2005 1797 1802 (Pubitemid 40223704)
16. E. Nemeth, M.S. Tuttle, J. Powelson, M.B. Vaughn, A. Donovan, D.M. Ward, T. Ganz, and J. Kaplan Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization Science 306 2004 2090 2093 (Pubitemid 40007660)
17. M.V. Verga Falzacappa, M. Vujic Spasic, R. Kessler, J. Stolte, M.W. Hentze, and M.U. Muckenthaler STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation Blood 109 2007 353 358 (Pubitemid 46053077)
18. J. Inamura, K. Ikuta, J. Jimbo, M. Shindo, K. Sato, Y. Torimoto, and Y. Kohgo Upregulation of hepcidin by interleukin-1beta in human hepatoma cell lines Hepatol. Res. 33 2005 198 205 (Pubitemid 41794207)
19. P. Lee, H. Peng, T. Gelbart, L. Wang, and E. Beutler Regulation of hepcidin transcription by interleukin-1 and interleukin-6 Proc. Natl. Acad. Sci. U.S.A. 102 2005 1906 1910 (Pubitemid 40261985)
20. A. Pietrangelo, U. Dierssen, L. Valli, C. Garuti, A. Rump, E. Corradini, M. Ernst, C. Klein, and C. Trautwein STAT3 is required for IL-6-gp130-dependent activation of hepcidin in vivo Gastroenterology 132 2007 294 300 (Pubitemid 46108739)
21. D.M. Wrighting, and N.C. Andrews Interleukin-6 induces hepcidin expression through STAT3 Blood 108 2006 3204 3209
22. G. Nicolas, C. Chauvet, L. Viatte, J.L. Danan, X. Bigard, I. Devaux, C. Beaumont, A. Kahn, and S. Vaulont The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation J. Clin. Invest. 110 2002 1037 1044
23. A.S. Zhang, J. Gao, D.D. Koeberl, and C.A. Enns The role of hepatocyte hemojuvelin in the regulation of bone morphogenic protein-6 and hepcidin expression in vivo J. Biol. Chem. 285 2010 16416 16423
24. T. Knittel, P. Fellmer, L. Muller, and G. Ramadori Bone morphogenetic protein-6 is expressed in nonparenchymal liver cells and upregulated by transforming growth factor-beta 1 Exp. Cell Res. 232 1997 263 269 (Pubitemid 27194038)
25. Y. Xia, J.L. Babitt, Y. Sidis, R.T. Chung, and H.Y. Lin Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin Blood 111 2008 5195 5204
26. G. Papanikolaou, M.E. Samuels, E.H. Ludwig, M.L. MacDonald, P.L. Franchini, M.P. Dube, L. Andres, J. MacFarlane, N. Sakellaropoulos, M. Politou, E. Nemeth, J. Thompson, J.K. Risler, C. Zaborowska, R. Babakaiff, C.C. Radomski, T.D. Pape, O. Davidas, J. Christakis, P. Brissot, G. Lockitch, T. Ganz, M.R. Hayden, and Y.P. Goldberg Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis Nat. Genet. 36 2004 77 82 (Pubitemid 38056211)
27. V. Niederkofler, R. Salie, and S. Arber Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload J. Clin. Invest. 115 2005 2180 2186 (Pubitemid 41134159)
28. L. Silvestri, A. Pagani, A. Nai, I. De Domenico, J. Kaplan, and C. Camaschella The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin Cell Metab. 8 2008 502 511
29. X. Du, E. She, T. Gelbart, J. Truksa, P. Lee, Y. Xia, K. Khovananth, S. Mudd, N. Mann, E.M. Moresco, E. Beutler, and B. Beutler The serine protease TMPRSS6 is required to sense iron deficiency Science 320 2008 1088 1092 (Pubitemid 351929552)
30. A.R. Folgueras, F.M. de Lara, A.M. Pendas, C. Garabaya, F. Rodriguez, A. Astudillo, T. Bernal, R. Cabanillas, C. Lopez-Otin, and G. Velasco Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis Blood 112 2008 2539 2545
31. K.E. Finberg, M.M. Heeney, D.R. Campagna, Y. Aydinok, H.A. Pearson, K.R. Hartman, M.M. Mayo, S.M. Samuel, J.J. Strouse, K. Markianos, N.C. Andrews, and M.D. Fleming Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia IRIDA Nat. Genet. 40 2008 569 571 (Pubitemid 351601217)
32. A.J. Ramsay, V. Quesada, M. Sanchez, C. Garabaya, M.P. Sarda, M. Baiget, A. Remacha, G. Velasco, and C. Lopez-Otin Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanisms Hum. Mol. Genet. 18 2009 3673 3683
33. I. Tchou, M. Diepold, P.A. Pilotto, D. Swinkels, M. Neerman-Arbez, and P. Beris Haematologic data, iron parameters and molecular findings in two new cases of iron-refractory iron deficiency anaemia Eur. J. Haematol. 83 2009 595 602
34. E. Beutler, C. Van Geet, D.M. te Loo, T. Gelbart, K. Crain, J. Truksa, and P.L. Lee Polymorphisms and mutations of human TMPRSS6 in iron deficiency anemia Blood Cells Mol. Dis. 44 2010 16 21
35. H.S. Choi, H.R. Yang, S.H. Song, J.Y. Seo, K.O. Lee, and H.J. Kim A novel mutation Gly603Arg of TMPRSS6 in a Korean female with iron-refractory iron deficiency anemia Epub Pediatr. Blood Cancer 2011
36. L. De Falco, F. Totaro, A. Nai, A. Pagani, D. Girelli, L. Silvestri, C. Piscopo, N. Campostrini, C. Dufour, F. Al Manjomi, M. Minkov, D.G. Van Vuurden, A. Feliu, A. Kattamis, C. Camaschella, and A. Iolascon Novel TMPRSS6 mutations associated with iron-refractory iron deficiency anemia IRIDA Hum. Mutat. 31 2010 E1390 E1405
37. L. Silvestri, F. Guillem, A. Pagani, A. Nai, C. Oudin, M. Silva, F. Toutain, C. Kannengiesser, C. Beaumont, C. Camaschella, and B. Grandchamp Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia Blood 113 2009 5605 5608
38. J. Truksa, P. Lee, and E. Beutler Two BMP responsive elements, STAT, and bZIP/HNF4/COUP motifs of the hepcidin promoter are critical for BMP, SMAD1, and HJV responsiveness Blood 113 2009 688 695
39. M.V. Verga Falzacappa, G. Casanovas, M.W. Hentze, and M.U. Muckenthaler A bone morphogenetic protein (BMP)-responsive element in the hepcidin promoter controls HFE2-mediated hepatic hepcidin expression and its response to IL-6 in cultured cells J. Mol. Med. 86 2008 531 540
40. R.H. Wang, C. Li, X. Xu, Y. Zheng, C. Xiao, P. Zerfas, S. Cooperman, M. Eckhaus, T. Rouault, L. Mishra, and C.X. Deng A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression Cell Metab. 2 2005 399 409
41. A.S. Zhang, S.A. Anderson, K.R. Meyers, C. Hernandez, R.S. Eisenstein, and C.A. Enns Evidence that inhibition of hemojuvelin shedding in response to iron is mediated through neogenin J. Biol. Chem. 282 2007 12547 12556 (Pubitemid 47100643)
42. A.S. Zhang, F. Yang, K. Meyer, C. Hernandez, T. Chapman-Arvedson, P.J. Bjorkman, and C.A. Enns Neogenin-mediated hemojuvelin shedding occurs after hemojuvelin traffics to the plasma membrane J. Biol. Chem. 283 2008 17494 17502
43. A.S. Zhang, F. Yang, J. Wang, H. Tsukamoto, and C.A. Enns Hemojuvelin-neogenin interaction is required for bone morphogenic protein-4-induced hepcidin expression J. Biol. Chem. 284 2009 22580 22589
44. D.H. Lee, L.J. Zhou, Z. Zhou, J.X. Xie, J.U. Jung, Y. Liu, C.X. Xi, L. Mei, and W.C. Xiong Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis Blood 115 2010 3136 3145
45. J.L. Babitt, F.W. Huang, D.M. Wrighting, Y. Xia, Y. Sidis, T.A. Samad, J.A. Campagna, R.T. Chung, A.L. Schneyer, C.J. Woolf, N.C. Andrews, and H.Y. Lin Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression Nat. Genet. 38 2006 531 539
46. L. Lin, E.V. Valore, E. Nemeth, J.B. Goodnough, V. Gabayan, and T. Ganz Iron-transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4 Blood 110 2007 2182 2189 (Pubitemid 47443938)
47. L. Kautz, D. Meynard, A. Monnier, V. Darnaud, R. Bouvet, R.H. Wang, C. Deng, S. Vaulont, J. Mosser, H. Coppin, and M.P. Roth Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver Blood 112 2008 1503 1509
48. A. Calzolari, C. Raggi, S. Deaglio, N.M. Sposi, M. Stafsnes, K. Fecchi, I. Parolini, F. Malavasi, C. Peschle, M. Sargiacomo, and U. Testa TfR2 localizes in lipid raft domains and is released in exosomes to activate signal transduction along the MAPK pathway J. Cell Sci. 119 2006 4486 4498 (Pubitemid 44830648)
49. M. Poli, S. Luscieti, V. Gandini, F. Maccarinelli, D. Finazzi, L. Silvestri, A. Roetto, and P. Arosio Transferrin receptor 2 and HFE regulate furin expression via mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) signaling. Implications for transferrin-dependent hepcidin regulation Haematologica 95 2010 1832 1840
50. E. Corradini, D. Meynard, Q. Wu, S. Chen, P. Ventura, A. Pietrangelo, and J.L. Babitt Serum and liver iron differently regulate the bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway in mice e-pub Hepatology 54 2011 273 274
51. E. Ramos, L. Kautz, R. Rodriguez, M. Hansen, V. Gabayan, Y. Ginzburg, M.P. Roth, E. Nemeth, and T. Ganz Evidence for distinct pathways of hepcidin regulation by acute and chronic iron loading in mice Hepatology 53 2011 1333 1341
52. G. Casanovas, K. Mleczko-Sanecka, S. Altamura, M.W. Hentze, and M.U. Muckenthaler Bone morphogenetic protein (BMP)-responsive elements located in the proximal and distal hepcidin promoter are critical for its response to HJV/BMP/SMAD J. Mol. Med. 87471-80 2009 471 480
53. A.U. Steinbicker, C. Sachidanandan, A.J. Vonner, R.Z. Yusuf, D.Y. Deng, C.S. Lai, K.M. Rauwerdink, J.C. Winn, B. Saez, C.M. Cook, B.A. Szekely, C.N. Roy, J.S. Seehra, G.D. Cuny, D.T. Scadden, R.T. Peterson, K.D. Bloch, and P.B. Yu Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation e-pub Blood 117 2011 4915 4923
54. M. Cazzola, Y. Beguin, G. Bergamaschi, R. Guarnone, P. Cerani, S. Barella, A. Cao, and R. Galanello Soluble transferrin receptor as a potential determinant of iron loading in congenital anaemias due to ineffective erythropoiesis Br. J. Haematol. 106 1999 752 755 (Pubitemid 29434218)
55. J.D. Cook, S. Dassenko, and B.S. Skikne Serum transferrin receptor as an index of iron absorption Brit J Haematol 75 1990 603 609 (Pubitemid 20271496)
56. R.A. Feelders, E.P. Kuiper-Kramer, and H.G. van Eijk Structure, function and clinical significance of transferrin receptors Clin. Chem. Lab. Med. 37 1999 1 10 (Pubitemid 29097247)
57. C.A. Flowers, M. Kuizon, J.L. Beard, B.S. Skikne, A.M. Covell, and J.D. Cook A serum ferritin assay for prevalence studies of iron deficiency Amer J Hematol 23 1986 141 151 (Pubitemid 16019885)
58. K.B. Raja, D.J. Pountney, R.J. Simpson, and T.J. Peters Importance of anemia and transferrin levels in the regulation of intestinal iron absorption in hypotransferrinemic mice Blood 94 1999 3185 3192 (Pubitemid 29512727)
59. P. Taylor, C. Martinez-Torres, I. Leets, J. Ramirez, M.N. Garcia-Casal, and M. Layrisse Relationships among iron absorption, percent saturation of plasma transferrin and serum ferritin concentration in humans J. Nutr. 118 1988 1110 1115
60. T.H. Bothwell, R.W. Charlton, and A.G. Motulsky The Metabolic and Molecular Basis of Inherited Disease, Seventh Edition ed 1995 McGraw-Hill, Inc San Francisco
61. S.E. Bernstein Hereditary hypotransferrinemia with hemosiderosis, a murine disorder resembling human atransferrinemia J. Lab. Clin. Med. 110 1987 690 705 (Pubitemid 18033263)
62. C. Beaumont, P. Leneuve, I. Devaux, J.Y. Scoazec, M. Berthier, M.N. Loiseau, B. Grandchamp, and D. Bonneau Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract Nat. Genet. 11 1995 444 446
63. D. Girelli, R. Corrocher, L. Bisceglia, O. Olivieri, F.L. De, L. Zelante, and P. Gasparini Molecular basis for the recently described hereditary hyperferritinemia-cataract syndrome: a mutation in the iron-responsive element of ferritin L-subunit gene the "Verona mutation" Blood 86 1995 4050 4053
64. S. R'Zik, M. Loo, and Y. Beguin Reticulocyte transferrin receptor (TfR) expression and contribution to soluble TfR levels Haematologica 86 2001 244 251 (Pubitemid 32291061)
65. A. Kattamis, I. Papassotiriou, D. Palaiologou, F. Apostolakou, A. Galani, V. Ladis, N. Sakellaropoulos, and G. Papanikolaou The effects of erythropoetic activity and iron burden on hepcidin expression in patients with thalassemia major Haematologica 91 2006 809 812 (Pubitemid 44014549)
66. G. Papanikolaou, M. Tzilianos, J.I. Christakis, D. Bogdanos, K. Tsimirika, J. MacFarlane, Y.P. Goldberg, N. Sakellaropoulos, T. Ganz, and E. Nemeth Hepcidin in iron overload disorders Blood 105 2005 4103 4105 (Pubitemid 40656161)
67. T. Tanno, N.V. Bhanu, P.A. Oneal, S.H. Goh, P. Staker, Y.T. Lee, J.W. Moroney, C.H. Reed, N.L. Luban, R.H. Wang, T.E. Eling, R. Childs, T. Ganz, S.F. Leitman, S. Fucharoen, and J.L. Miller High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin Nat. Med. 13 2007 1096 1101 (Pubitemid 47517510)
68. T. Tanno, P. Noel, and J.L. Miller Growth differentiation factor 15 in erythroid health and disease Curr. Opin. Hematol. 17 2010 184 190
69. T. Tanno, A. Porayette, S. Orapan, S.-J. Noh, C. Byrnes, A. Bhupatiraju, Y.T. Lee, J.B. Goodnough, O. Harandi, T. Ganz, R.F. Paulson, and J.L. Miller Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells Blood 114 2009 181 186
70. S. Hara-Kuge, T. Ohkura, H. Ideo, O. Shimada, S. Atsumi, and K. Yamashita Involvement of VIP36 in intracellular transport and secretion of glycoproteins in polarized Madin-Darby canine kidney (MDCK) cells J. Biol. Chem. 277 2002 16332 16339 (Pubitemid 34967922)
71. Z.L. Harris, A.P. Durley, T.K. Man, and J.D. Gitlin Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux Proc. Natl. Acad. Sci. U.S.A. 96 1999 10812 10817 (Pubitemid 29442226)
72. Z.L. Harris, Y. Takahashi, H. Miyajima, M. Serizawa, R.T. MacGillivray, and J.D. Gitlin Aceruloplasminemia: molecular characterization of this disorder of iron metabolism Proc. Natl. Acad. Sci. U.S.A. 92 1995 2539 2543
73. J. Sarkar, V. Seshadri, N.A. Tripoulas, M.E. Ketterer, and P.L. Fox Role of ceruloplasmin in macrophage iron efflux during hypoxia J. Biol. Chem. 278 2003 44018 44024 (Pubitemid 37377141)
74. H. Kawabata, R.S. Germain, P.T. Vuong, T. Nakamaki, J.W. Said, and H.P. Koeffler Transferrin receptor 2-alpha supports cell growth both in iron-chelated cultured cells and in vivo J. Biol. Chem. 275 2000 16618 16625 (Pubitemid 30398888)
75. A. Smith, and R.C. Hunt Hemopexin joins transferrin as representative members of a distinct class of receptor-mediated endocytic transport systems Eur. J. Cell Biol. 53 1990 234 245
76. J.P. Kushner, J.P. Porter, and N.F. Olivieri Secondary iron overload Hematology (Am Soc Hematol Educ Program) 2001 47 61
77. L.W. Powell, C.B. Campbell, and E. Wilson Intestinal mucosal uptake of iron and iron retention in idiopathic haemochromatosis as evidence for a mucosal abnormality Gut 11 1970 727 731
78. T. Cox Haemochromatosis: strike while the iron is hot Nat. Genet. 13 1996 386 388
79. P.C. Adams, D.M. Reboussin, J.C. Barton, C.E. McLaren, J.H. Eckfeldt, G.D. McLaren, F.W. Dawkins, R.T. Acton, E.L. Harris, V.R. Gordeuk, C. Leiendecker-Foster, M. Speechley, B.M. Snively, J.L. Holup, E. Thomson, and P. Sholinsky Hemochromatosis and iron-overload screening in a racially diverse population N. Engl. J. Med. 352 2005 1769 1778 (Pubitemid 40570925)
80. R.E. Fleming, C.C. Holden, S. Tomatsu, A. Waheed, E.M. Brunt, R.S. Britton, B.R. Bacon, D.C. Roopenian, and W.S. Sly Mouse strain differences determine severity of iron accumulation in Hfe knockout model of hereditary hemochromatosis Proc. Natl. Acad. Sci. U.S.A. 98 2001 2707 2711 (Pubitemid 32209547)
81. D. Girelli, C. Bozzini, A. Roetto, F. Alberti, F. Daraio, R. Colombari, O. Olivieri, R. Corrocher, and C. Camaschella Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene Gastroenterology 122 2002 1295 1302 (Pubitemid 34465172)
82. A. Roetto, G. Papanikolaou, M. Politou, F. Alberti, D. Girelli, J. Christakis, D. Loukopoulos, and C. Camaschella Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis Nat. Genet. 33 2003 21 22 (Pubitemid 36068676)
83. A. Roetto, A. Totaro, M. Cazzola, M. Cicilano, S. Bosio, G. D'Ascola, M. Carella, L. Zelante, A.L. Kelly, T.M. Cox, P. Gasparini, and C. Camaschella Juvenile hemochromatosis locus maps to chromosome 1q Am. J. Hum. Genet. 64 1999 1388 1393 (Pubitemid 30468757)
84. I. De Domenico, D.M. Ward, G. Musci, and J. Kaplan Iron overload due to mutations in ferroportin Haematologica 91 2006 92 95 (Pubitemid 43235391)
85. E.E. Johnson, and M. Wessling-Resnick Flatiron mice and ferroportin disease Nutr. Rev. 65 2007 341 345 (Pubitemid 351804359)
86. I.E. Zohn, I. De Domenico, A. Pollock, D.M. Ward, J.F. Goodman, X. Liang, A.J. Sanchez, L. Niswander, and J. Kaplan The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease Blood 109 2007 4174 4180 (Pubitemid 46743381)
87. P. Aisen, C. Enns, and M. Wessling-Resnick Chemistry and biology of eukaryotic iron metabolism Int. J. Biochem. Cell Biol. 33 2001 940 959 (Pubitemid 32706687)
88. P.K. Bali, and P. Aisen Receptor-modulated iron release from transferrin: differential effects on N- and C-terminal sites Biochemistry 30 1991 9947 9952
89. D.M. Sipe, and R.F. Murphy Binding to cellular receptor results in increased iron release from transferrin at mildly acidic pH J. Biol. Chem. 266 1991 8002 8007 (Pubitemid 21906466)
90. C. Camaschella, A. Roetto, A. Cali, M. De Gobbi, G. Garozzo, M. Carella, N. Majorano, A. Totaro, and P. Gasparini The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22 Nat. Genet. 25 2000 14 15 (Pubitemid 30257027)
91. C.E. Herbison, K. Thorstensen, A.C. Chua, R.M. Graham, P. Leedman, J.K. Olynyk, and D. Trinder The role of transferrin receptor 1 and 2 in transferrin-bound iron uptake in human hepatoma cells Am. J. Physiol. Cell Physiol. 297 2009 C1567 C1575
92. D.F. Wallace, L. Summerville, P.E. Lusby, and V.N. Subramaniam First phenotypic description of transferrin receptor 2 knockout mouse, and the role of hepcidin Gut 54 2005 980 986 (Pubitemid 40873913)
93. R.E. Fleming, J.R. Ahmann, M.C. Migas, A. Waheed, H.P. Koeffler, H. Kawabata, R.S. Britton, B.R. Bacon, and W.S. Sly Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis Proc. Natl. Acad. Sci. U.S.A. 99 2002 10653 10658
94. U. Merle, F. Theilig, E. Fein, S. Gehrke, B. Kallinowski, H.D. Riedel, S. Bachmann, W. Stremmel, and H. Kulaksiz Localization of the iron-regulatory proteins hemojuvelin and transferrin receptor 2 to the basolateral membrane domain of hepatocytes Histochem. Cell Biol. 127 2007 221 226 (Pubitemid 46147276)
95. A.S. Zhang, S. Xiong, H. Tsukamoto, and C.A. Enns Localization of iron metabolism-related mRNAs in rat liver indicate that HFE is expressed predominantly in hepatocytes Blood 103 2004 1509 1514 (Pubitemid 38168670)
96. M.B. Johnson, and C.A. Enns Diferric transferrin regulates transferrin receptor 2 protein stability Blood 104 2004 4287 4293 (Pubitemid 39620184)
97. R.E. Fleming, M.C. Migas, C.C. Holden, A. Waheed, R.S. Britton, S. Tomatsu, B.R. Bacon, and W.S. Sly Transferrin receptor 2: continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis Proc. Natl. Acad. Sci. U.S.A. 97 2000 2214 2219 (Pubitemid 30134048)
98. H. Kawabata, R. Yang, T. Hirama, P.T. Vuong, S. Kawano, A.F. Gombart, and H.P. Koeffler Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family J. Biol. Chem. 274 1999 20826 20832
99. N.M. Sposi, L. Cianetti, E. Tritarelli, E. Pelosi, S. Militi, T. Barberi, M. Gabbianelli, E. Saulle, L. Kuhn, C. Peschle, and U. Testa Mechanisms of differential transferrin receptor expression in normal hematopoiesis Eur. J. Biochem. 267 2000 6762 6774
100. H. Kawabata, T. Nakamaki, P. Ikonomi, R.D. Smith, R.S. Germain, and H.P. Koeffler Expression of transferrin receptor 2 in normal and neoplastic hematopoietic cells Blood 98 2001 2714 2719
101. A. Robb, and M. Wessling-Resnick Regulation of transferrin receptor 2 protein levels by transferrin Blood 104 2004 4294 4299 (Pubitemid 39620185)
102. H. Kawabata, R.S. Germain, T. Ikezoe, X. Tong, E.M. Green, A.F. Gombart, and H.P. Koeffler Regulation of expression of murine transferrin receptor 2 Blood 98 2001 1949 1954
103. J.E. Levy, O. Jin, Y. Fujiwara, F. Kuo, and N.C. Andrews Transferrin receptor is necessary for development of erythrocytes and the nervous system Nat. Genet. 21 1999 396 399 (Pubitemid 29159576)
104. H. Kawabata, X. Tong, T. Kawanami, Y. Wano, Y. Hirose, S. Sugai, and H.P. Koeffler Analyses for binding of the transferrin family of proteins to the transferrin receptor 2 Br. J. Haematol. 127 2004 464 473 (Pubitemid 39536600)
105. A.P. West Jr. , M.J. Bennett, V.M. Sellers, N.C. Andrews, C.A. Enns, and P.J. Bjorkman Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE J. Biol. Chem. 275 2000 38135 38138 (Pubitemid 32009130)
106. J. Chen, J. Wang, K.R. Meyers, and C.A. Enns Transferrin-directed internalization and cycling of transferrin receptor 2 Traffic 10 2009 1488 1501
107. M.J. Bennett, J.A. Lebron, and P.J. Bjorkman Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor Nature 403 2000 46 53 (Pubitemid 30038514)
108. A.M. Giannetti, and P.J. Bjorkman HFE and transferrin directly compete for transferrin receptor in solution and at the cell surface J. Biol. Chem. 279 2004 25866 25875 (Pubitemid 38756852)
109. A.P. West Jr. , A.M. Giannetti, A.B. Herr, M.J. Bennett, J.S. Nangiana, J.R. Pierce, L.P. Weiner, P.M. Snow, and P.J. Bjorkman Mutational Analysis of the Transferrin Receptor Reveals Overlapping HFE and Transferrin Binding Sites J. Mol. Biol. 313 2001 385 397 (Pubitemid 33587195)
110. J. Chen, M. Chloupkova, J. Gao, T.L. Chapman-Arvedson, and C.A. Enns HFE modulates transferrin receptor 2 levels in hepatoma cells via interactions that differ from transferrin receptor 1-HFE interactions J. Biol. Chem. 282 2007 36862 36870
111. T. Goswami, and N.C. Andrews Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing J. Biol. Chem. 281 2006 28494 28498 (Pubitemid 44506991)
112. J. Gao, J. Chen, I. De Domenico, D.M. Koeller, C.O. Harding, R.E. Fleming, D.D. Koeberl, and C.A. Enns Hepatocyte-targeted HFE and TFR2 control hepcidin expression in mice Blood 115 2010 3374 3381
113. J. Gao, J. Chen, M. Kramer, H. Tsukamoto, A.S. Zhang, and C.A. Enns Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression Cell Metab. 9 2009 217 227
114. S. Deaglio, A. Capobianco, A. Cali, F. Bellora, F. Alberti, L. Righi, A. Sapino, C. Camaschella, and F. Malavasi Structural, functional, and tissue distribution analysis of human transferrin receptor-2 by murine monoclonal antibodies and a polyclonal antiserum Blood 100 2002 3782 3789 (Pubitemid 35303952)
115. W.J. Griffiths, and T.M. Cox Co-localization of the mammalian hemochromatosis gene product (HFE) and a newly identified transferrin receptor (TfR2) in intestinal tissue and cells J. Histochem. Cytochem. 51 2003 613 624
116. G. Biasiotto, S. Belloli, G. Ruggeri, I. Zanella, G. Gerardi, M. Corrado, E. Gobbi, A. Albertini, and P. Arosio Identification of new mutations of the HFE, hepcidin, and transferrin receptor 2 genes by denaturing HPLC analysis of individuals with biochemical indications of iron overload Clin. Chem. 49 2003 1981 1988 (Pubitemid 37449469)
117. D.F. Wallace, L. Summerville, and V.N. Subramaniam Targeted disruption of the hepatic transferrin receptor 2 gene in mice leads to iron overload Gastroenterology 132 2007 301 310 (Pubitemid 46108757)
118. A. Roetto, F. Di Cunto, R.M. Pellegrino, E. Hirsch, O. Azzolino, A. Bondi, I. Defilippi, S. Carturan, B. Miniscalco, F. Riondato, D. Cilloni, L. Silengo, F. Altruda, C. Camaschella, and G. Saglio Comparison of 3 Tfr2-deficient murine models suggests distinct functions for Tfr2-alpha and Tfr2-beta isoforms in different tissues Blood 115 2010 3382 3389
119. J. Chen, and C.A. Enns The cytoplasmic domain of transferrin receptor 2 dictates its stability and response to holo-transferrin in Hep3B cells J. Biol. Chem. 282 2007 6201 6209 (Pubitemid 47100900)
120. M.B. Johnson, J. Chen, N. Murchison, F.A. Green, and C.A. Enns Transferrin receptor 2: evidence for ligand-induced stabilization and redirection to a recycling pathway Mol. Biol. Cell 18 2007 743 754 (Pubitemid 46399482)
121. C. Rapisarda, J. Puppi, R.D. Hughes, A. Dhawan, S. Farnaud, R.W. Evans, and P.A. Sharp Transferrin receptor 2 is crucial for iron sensing in human hepatocytes Am. J. Physiol. Gastrointest. Liver Physiol. 299 2010 G778 G783
122. D. Girelli, P. Trombini, F. Busti, N. Campostrini, M. Sandri, S. Pelucchi, M. Westerman, T. Ganz, E. Nemeth, A. Piperno, and C. Camaschella A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis Haematologica 96 2011 500 506
123. P.J. Schmidt, P.T. Toran, A.M. Giannetti, P.J. Bjorkman, and N.C. Andrews The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression Cell Metab. 7 2008 205 214 (Pubitemid 351285524)
124. A. Piperno, D. Girelli, E. Nemeth, P. Trombini, C. Bozzini, E. Poggiali, Y. Phung, T. Ganz, and C. Camaschella Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis Blood 110 2007 4096 4100 (Pubitemid 350248467)
125. S. Gehrke, A. Pietrangelo, M. Kascak, A. Braner, M. Eisold, H. Kulaksiz, T. Herrmann, U. Hebling, K. Bents, R. Gugler, and W. Stremmel HJV gene mutations in European patients with juvenile hemochromatosis Clin. Genet. 67 2005 425 428 (Pubitemid 40561493)
126. D.F. Wallace, L. Summerville, E.M. Crampton, D.M. Frazer, G.J. Anderson, and V.N. Subramaniam Combined deletion of Hfe and transferrin receptor 2 in mice leads to marked dysregulation of hepcidin and iron overload Hepatology 50 2009 1992 2000
127. A. Pietrangelo, A. Caleffi, J. Henrion, F. Ferrara, E. Corradini, H. Kulaksiz, W. Stremmel, P. Andreone, and C. Garuti Juvenile hemochromatosis associated with pathogenic mutations of adult hemochromatosis genes Gastroenterology 128 2005 470 479 (Pubitemid 40431098)
128. J.L. Babitt, F.W. Huang, Y. Xia, Y. Sidis, N.C. Andrews, and H.Y. Lin Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance J. Clin. Invest. 117 2007 1933 1939 (Pubitemid 47036327)
129. D. Meynard, L. Kautz, V. Darnaud, F. Canonne-Hergaux, H. Coppin, and M.P. Roth Lack of the bone morphogenetic protein BMP6 induces massive iron overload Nat. Genet. 41 2009 478 481
130. B. Andriopoulos Jr. , E. Corradini, Y. Xia, S.A. Faasse, S. Chen, L. Grgurevic, M.D. Knutson, A. Pietrangelo, S. Vukicevic, H.Y. Lin, and J.L. Babitt BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism Nat. Genet. 41 2009 482 487
131. L. Kautz, D. Meynard, C. Besson-Fournier, V. Darnaud, T. Al Saati, H. Coppin, and M.P. Roth BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression Blood 114 2009 2515 2520
132. E. Corradini, C. Garuti, G. Montosi, P. Ventura, B. Andriopoulos Jr. , H.Y. Lin, A. Pietrangelo, and J.L. Babitt Bone morphogenetic protein signaling is impaired in an HFE knockout mouse model of hemochromatosis Gastroenterology 137 2009 1489 1497
133. G. Ramey, J.C. Deschemin, and S. Vaulont Cross-talk between the mitogen activated protein kinase and bone morphogenetic protein/hemojuvelin pathways is required for the induction of hepcidin by holotransferrin in primary mouse hepatocytes Haematologica 94 2009 765 772
134. P. Kollia, M. Samara, K. Stamatopoulos, C. Belessi, N. Stavroyianni, A. Tsompanakou, A. Athanasiadou, N. Vamvakopoulos, N. Laoutaris, A. Anagnostopoulos, and A. Fassas Molecular evidence for transferrin receptor 2 expression in all FAB subtypes of acute myeloid leukemia Leuk. Res. 27 2003 1101 1103 (Pubitemid 36960030)
135. H. Forejtnikova, M. Vieillevoye, Y. Zermati, M. Lambert, R.M. Pellegrino, S. Guihard, M. Gaudry, C. Camaschella, C. Lacombe, A. Roetto, P. Mayeux, and F. Verdier Transferrin receptor 2 is a component of the erythropoietin receptor complex and is required for efficient erythropoiesis Blood 116 2010 5357 5367
136. S.K. Ganesh, N.A. Zakai, F.J. van Rooij, N. Soranzo, A.V. Smith, M.A. Nalls, M.H. Chen, A. Kottgen, N.L. Glazer, A. Dehghan, B. Kuhnel, T. Aspelund, Q. Yang, T. Tanaka, A. Jaffe, J.C. Bis, G.C. Verwoert, A. Teumer, C.S. Fox, J.M. Guralnik, G.B. Ehret, K. Rice, J.F. Felix, A. Rendon, G. Eiriksdottir, D. Levy, K.V. Patel, E. Boerwinkle, J.I. Rotter, A. Hofman, J.G. Sambrook, D.G. Hernandez, G. Zheng, S. Bandinelli, A.B. Singleton, J. Coresh, T. Lumley, A.G. Uitterlinden, J.M. Vangils, L.J. Launer, L.A. Cupples, B.A. Oostra, J.J. Zwaginga, W.H. Ouwehand, S.L. Thein, C. Meisinger, P. Deloukas, M. Nauck, T.D. Spector, C. Gieger, V. Gudnason, C.M. van Duijn, B.M. Psaty, L. Ferrucci, A. Chakravarti, A. Greinacher, C.J. O'Donnell, J.C. Witteman, S. Furth, M. Cushman, T.B. Harris, and J.P. Lin Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium Nat. Genet. 41 2009 1191 1198
137. H. Wu, X. Liu, R. Jaenisch, and H.F. Lodish Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor Cell 83 1995 59 67
138. E. Ingley, P.A. Tilbrook, and S.P. Klinken New insights into the regulation of erythroid cells IUBMB Life 56 2004 177 184 (Pubitemid 38828745)
139. P. Sathyanarayana, A. Dev, J. Fang, E. Houde, O. Bogacheva, O. Bogachev, M. Menon, S. Browne, A. Pradeep, C. Emerson, and D.M. Wojchowski EPO receptor circuits for primary erythroblast survival Blood 111 2008 5390 5399