Furin-mediated release of soluble hemojuvelin: A new link between hypoxia and iron homeostasis

Blood

Volumn 111, Issue 2, 2008, Pages 924-931

  Silvestri, Laura ^a   Pagani, Alessia ^a   Camaschella, Clara ^a  

^a VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

FURIN; HEMOJUVELIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA;

ARTICLE; CELL DIFFERENTIATION; CONTROLLED STUDY; HOMEOSTASIS; HUMAN; HUMAN CELL; HYPOXIA; IRON DEFICIENCY; IRON METABOLISM; LIVER; MUSCLE CELL; OXYGEN TISSUE LEVEL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SECRETION; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; TISSUE SPECIFICITY; UPREGULATION;

EID: 38349194098     PISSN: 00064971     EISSN: 00064971     Source Type: Journal    
DOI: 10.1182/blood-2007-07-100677     Document Type: Article

References (35)

1. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003;102:783-788.
2. Papanikolaou G, Samuels ME, Ludwig EH, et al. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet. 2004;36:77-82.
3. Niederkofler V, Salie R, Arber S. Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload. J Clin Invest. 2005;115:2180-2186.
4. Huang FW, Pinkus JL, Pinkus GS, Fleming MD, Andrews NC. A mouse model of juvenile hemochromatosis. J Clin Invest. 2005;115:2187-2191.
5. Matsunaga E, Chedotal A. Repulsive guidance molecule/neogenin: a novel ligand-receptor system playing multiple roles in neural development. Dev Growth Differ. 2004;46:481-486.
6. Matsunaga E, Nakamura H, Chedotal A. Repulsive guidance molecule plays multiple roles in neuronal differentiation and axon guidance. J Neurosci. 2006;26:6082-6088.
7. Lin L, Goldberg YP, Ganz T. Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin. Blood. 2005;106:2884-2889.
8. Kuninger D, Kuns-Hashimoto R, Kuzmickas R, Rotwein P. Complex biosynthesis of the muscle-enriched iron regulator RGMc. J Cell Sci. 2006;119:3273-3283.
9. Silvestri L, Pagani A, Fazi C, et al. Defective targeting of hemojuvelin to plasma membrane is a common pathogenetic mechanism in juvenile hemochromatosis. Blood. 2007;109:4503-4510.
10. Babitt JL, Huang FW, Wrighting DM, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38:531-539.
11. 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;2:399-409.
12. Lin L, Valore EV, Nemeth E, Goodnough JB, Gabayan V, Ganz T. Iron transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4. Blood. 2007;110:2182-2189.
13. 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;117:1933-1939.
14. Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994;22:4673-4680.
15. Lotti LV, Mottola G, Torrisi MR, Bonatti S. A different intracellular distribution of a single reporter protein is determined at steady state by KKXX or KDEL retrieval signals. J Biol Chem. 1999;274:10413-10420.
16. Takahashi S, Nakagawa T, Kasai K, et al. A second mutant allele of furin in the processing-incompetent cell line, LoVo: evidence for involvement of the homo B domain in autocatalytic activation. J Biol Chem. 1995;270:26565-26569.
17. McMahon S, Grondin F, McDonald PP, Richard DE, Dubois CM. Hypoxia-enhanced expression of the proprotein convertase furin is mediated by hypoxia-inducible factor-1: impact on the bioactivation of proproteins. J Biol Chem. 2005;280:6561-6569.
18. Polishchuk EV, Di Pentima A, Luini A, Polishchuk RS. Mechanism of constitutive export from the golgi: bulk flow via the formation, protrusion, and en bloc cleavage of large trans-golgi network tubular domains. Mol Biol Cell. 2003;14:4470-4485.
19. Puntervoll P, Linding R, Gemund C, et al. ELM server: a new resource for investigating short functional sites in modular eukaryotic proteins. Nucleic Acids Res. 2003;31:3625-3630.
20. Duckert P, Brunak S, Blom N. Prediction of proprotein convertase cleavage sites. Protein Eng Des Sel. 2004;17:107-112.
21. Lin L, Nemeth E, Goodnough JB, Thapa DR, Gabayan V, Ganz T. Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site. Blood Cells Mol Dis. 2008;40:122-131.
22. Hamrick SE, McQuillen PS, Jiang X, Mu D, Madan A, Ferriero DM. A role for hypoxia-inducible factor-1alpha in desferoxamine neuroprotection. Neurosci Lett. 2005;379:96-100.
23. Templeton DM, Liu Y. Genetic regulation of cell function in response to iron overload or chelation. Biochim Biophys Acta. 2003;1619:113-124.
24. Zhang AS, West AP Jr, Wyman AE, Bjorkman PJ, Enns CA. Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells. J Biol Chem. 2005;280:33885-33894.
25. Lanzara C, Roetto A, Daraio F, et al. Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis. Blood. 2004;103:4317-4321.
26. Zhang AS, Anderson SA, Meyers KR, Hernandez C, Eisenstein RS, Enns CA. Evidence that inhibition of hemojuvelin shedding in response to iron is mediated through neogenin. J Biol Chem. 2007;282:12547-12556.
27. Semenza GL. HIF-1 and mechanisms of hypoxia sensing. Curr Opin Cell Biol. 2001;13:167-171.
28. Ono Y, Sensui H, Sakamoto Y, Nagatomi R. Knockdown of hypoxia-inducible factor-1alpha by siRNA inhibits C2C12 myoblast differentiation. J Cell Biochem. 2006;98:642-649.
29. Wittenberg JB, Wittenberg BA. Myoglobin function reassessed. J Exp Biol. 2003;206:2011-2020.
30. Ordway GA, Garry DJ. Myoglobin: an essential hemoprotein in striated muscle. J Exp Biol. 2004;207:3441-3446.
31. Ameln H, Gustafsson T, Sundberg CJ, et al. Physiological activation of hypoxia inducible factor-1 in human skeletal muscle. Faseb J. 2005;19:1009-1011.
32. Lundby C, Gassmann M, Pilegaard H. Regular endurance training reduces the exercise induced HIF-1alpha and HIF-2alpha mRNA expression in human skeletal muscle in normoxic conditions. Eur J Appl Physiol. 2006;96:363-369.
33. Salvas A, Benjannet S, Reudelhuber TL, Chrétien M, Seidah NG. Evidence for proprotein convertase activity in the endoplasmic reticulum/early Golgi. FEBS Lett. 2005;579:5621-5625.
34. Le Gac G, Scotet V, Ka C, et al. The recently identified type 2A juvenile haemochromatosis gene (HJV), a second candidate modifier of the C282Y homozygous phenotype. Hum Mol Genet. 2004;13:1913-1918.
35. Peyssonnaux C, Zinkernagel AS, Schuepbach RA, et al. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest. 2007;117:1926-1932.