HFE interacts with the BMP type I receptor ALK3 to regulate hepcidin expression

Blood

Volumn 124, Issue 8, 2014, Pages 1335-1343

  Wu, Xing Gang ^a   Wang, Yang ^a   Wu, Qian ^b   Cheng, Wai Hang ^a   Liu, Wenjing ^a   Zhao, Yueshui ^a   Mayeur, Claire ^c   Schmidt, Paul J ^d   Yu, Paul B ^e   Wang, Fudi ^b   Xia, Yin ^a  

^a CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^b ZHEJIANG UNIVERSITY   (China)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d BOSTON CHILDREN S HOSPITAL   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN RECEPTOR 1A; HEPCIDIN; HFE PROTEIN; SMAD1 PROTEIN; SMAD5 PROTEIN; SMAD8 PROTEIN;

ANIMAL TISSUE; ARTICLE; CELL LEVEL; CELL SURFACE; CONTROLLED STUDY; GENE DELETION; GENE EXPRESSION REGULATION; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; UBIQUITINATION;

AMINO ACID SUBSTITUTION; ANIMALS; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE I; CERCOPITHECUS AETHIOPS; COS CELLS; GENE EXPRESSION REGULATION; HEP G2 CELLS; HEPCIDINS; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; MATRIX METALLOPROTEINASES, SECRETED; MEMBRANE PROTEINS; MICE; MICE, KNOCKOUT; MUTATION, MISSENSE; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEOLYSIS; SMAD PROTEINS; UBIQUITINATION;

EID: 84907321174     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2014-01-552281     Document Type: Article

References (35)

1. Pietrangelo A. Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology. 2010;139(2):393-408, e1-e2.
2. Ganz T. Hepcidin and iron regulation, 10 years later. Blood. 2011;117(17):4425-4433.
3. Andrews NC. Closing the iron gate. N Engl J Med. 2012;366(4):376-377.
4. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090-2093. (Pubitemid 40007660)
5. Wang RH, Li C, Xu X, et al. A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression. Cell Metab. 2005;2(6):399-409.
6. Babitt JL, Huang FW, Wrighting DM, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38(5):531-539.
7. Xia Y, Babitt JL, Sidis Y, Chung RT, Lin HY. Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin. Blood. 2008;111(10):5195-5204.
8. Andriopoulos B Jr, Corradini E, Xia Y, et al. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet. 2009;41(4):482-487.
9. Meynard D, Kautz L, Darnaud V, Canonne-Hergaux F, Coppin H, Roth MP. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet. 2009;41(4):478-481.
10. Shi Y, Massagué J. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell. 2003;113(6):685-700. (Pubitemid 36724933)
11. Truksa J, Peng H, Lee P, Beutler E. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proc Natl Acad Sci U S A. 2006;103(27):10289-10293. (Pubitemid 44051159)
12. Babitt JL, Huang FW, Xia Y, Sidis Y, Andrews NC, Lin HY. Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance. J Clin Invest. 2007;117(7):1933-1939. (Pubitemid 47036327)
13. Steinbicker AU, Bartnikas TB, Lohmeyer LK, et al. Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice. Blood. 2011;118(15):4224-4230.
14. Steinbicker AU, Sachidanandan C, Vonner AJ, et al. Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation. Blood. 2011;117(18):4915-4923.
15. Schmidt PJ, Toran PT, Giannetti AM, Bjorkman PJ, Andrews NC. The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression. Cell Metab. 2008;7(3):205-214. (Pubitemid 351285524)
16. Wallace DF, Summerville L, Crampton EM, Frazer DM, Anderson GJ, Subramaniam VN. Combined deletion of Hfe and transferrin receptor 2 in mice leads to marked dysregulation of hepcidin and iron overload. Hepatology. 2009;50(6):1992-2000.
17. Gao J, Chen J, De Domenico I, et al. Hepatocyte-targeted HFE and TFR2 control hepcidin expression in mice. Blood. 2010;115(16):3374-3381.
18. Schmidt PJ, Andrews NC, Fleming MD. Hepcidin induction by transgenic overexpression of Hfe does not require the Hfe cytoplasmic tail, but does require hemojuvelin. Blood. 2010;116(25):5679-5687.
19. Corradini E, Rozier M, Meynard D, et al. Iron regulation of hepcidin despite attenuated Smad1,5,8 signaling in mice without transferrin receptor 2 or Hfe. Gastroenterology. 2011;141(5):1907-1914.
20. West AP Jr, Bennett MJ, Sellers VM, Andrews NC, Enns CA, Bjorkman PJ. Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. J Biol Chem. 2000;275(49):38135-38138. (Pubitemid 32009130)
21. Goswami T, Andrews NC. Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. J Biol Chem. 2006;281(39):28494-28498. (Pubitemid 44506991)
22. Gao J, Chen J, Kramer M, Tsukamoto H, Zhang AS, Enns CA. Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression. Cell Metab. 2009;9(3):217-227.
23. D'Alessio F, Hentze MW, Muckenthaler MU. The hemochromatosis proteins HFE, TfR2, and HJV form a membrane-associated protein complex for hepcidin regulation. J Hepatol. 2012;57(5):1052-1060.
24. Schmidt PJ, Fleming MD. Transgenic HFE-dependent induction of hepcidin in mice does not require transferrin receptor-2. Am J Hematol. 2012;87(6):588-595.
25. Rishi G, Crampton EM, Wallace DF, Subramaniam VN. In situ proximity ligation assays indicate that hemochromatosis proteins Hfe and transferrin receptor 2 (Tfr2) do not interact. PLoS ONE. 2013;8(10):e77267.
26. Corradini E, Garuti C, Montosi G, et al. Bone morphogenetic protein signaling is impaired in an HFE knockout mouse model of hemochromatosis. Gastroenterology. 2009;137(4):1489-1497.
27. Kautz L, Meynard D, Besson-Fournier C, et al. BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression. Blood. 2009;114(12):2515-2520.
28. Ryan JD, Ryan E, Fabre A, Lawless MW, Crowe J. Defective bone morphogenic protein signaling underlies hepcidin deficiency in HFE hereditary hemochromatosis. Hepatology. 2010;52(4):1266-1273.
29. Bolondi G, Garuti C, Corradini E, et al. Altered hepatic BMP signaling pathway in human HFE hemochromatosis. Blood Cells Mol Dis. 2010;45(4):308-312.
30. Xia Y, Cortez-Retamozo V, Niederkofler V, et al. Dragon (repulsive guidance molecule b) inhibits IL-6 expression in macrophages. J Immunol. 2011;186(3):1369-1376.
31. Feder JN, Tsuchihashi Z, Irrinki A, et al. The hemochromatosis founder mutation in HLA-H disrupts beta2-microglobulin interaction and cell surface expression. J Biol Chem. 1997;272(22):14025-14028. (Pubitemid 27232800)
32. Waheed A, Parkkila S, Zhou XY, 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(23):12384-12389.
33. Lebrón JA, Bennett MJ, Vaughn DE, et al. Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell. 1998;93(1):111-123. (Pubitemid 28173557)
34. Murakami G, Watabe T, Takaoka K, Miyazono K, Imamura T. Cooperative inhibition of bone morphogenetic protein signaling by Smurf1 and inhibitory Smads. Mol Biol Cell. 2003;14(7):2809-2817. (Pubitemid 36871523)
35. Murakami K, Mathew R, Huang J, et al. Smurf1 ubiquitin ligase causes downregulation of BMP receptors and is induced in monocrotaline and hypoxia models of pulmonary arterial hypertension. Exp Biol Med (Maywood). 2010;235(7):805-813.