Identification of TMPRSS6 cleavage sites of hemojuvelin

Journal of Cellular and Molecular Medicine

Volumn 19, Issue 4, 2015, Pages 879-888

  Rausa, Marco ^a,b   Ghitti, Michela ^a   Pagani, Alessia ^a,b   Nai, Antonella ^a,b   Campanella, Alessandro ^a,b   Musco, Giovanna ^a   Camaschella, Clara ^a,b   Silvestri, Laura ^a,b  

^a SAN RAFFAELE HOSPITAL   (Italy)

^b VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

Author keywords

Hepcidin; HJV; Homology modelling; Iron; RGM; Serine protease; TMPRSS6

Indexed keywords

ARGININE; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORED PROTEIN; HFE2 PROTEIN, HUMAN; MEMBRANE PROTEIN; MUTANT PROTEIN; PROTEIN BINDING; SERINE PROTEINASE; TMPRSS6 PROTEIN, HUMAN;

AMINO ACID SEQUENCE; BINDING SITE; CELL MEMBRANE; CHEMISTRY; GENETICS; HELA CELL LINE; HUMAN; HYDROGEN BOND; METABOLISM; MISSENSE MUTATION; MOLECULAR DYNAMICS; MOLECULAR GENETICS; POLYACRYLAMIDE GEL ELECTROPHORESIS; PROTEIN DEGRADATION; PROTEIN MULTIMERIZATION; PROTEIN TERTIARY STRUCTURE; TUMOR CELL LINE;

AMINO ACID SEQUENCE; ARGININE; BINDING SITES; CELL LINE, TUMOR; CELL MEMBRANE; ELECTROPHORESIS, POLYACRYLAMIDE GEL; GPI-LINKED PROTEINS; HELA CELLS; HUMANS; HYDROGEN BONDING; MEMBRANE PROTEINS; MOLECULAR DYNAMICS SIMULATION; MOLECULAR SEQUENCE DATA; MUTANT PROTEINS; MUTATION, MISSENSE; PROTEIN BINDING; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, TERTIARY; PROTEOLYSIS; SERINE ENDOPEPTIDASES;

EID: 84925947135     PISSN: 15821838     EISSN: None     Source Type: Journal    
DOI: 10.1111/jcmm.12462     Document Type: Article

References (32)

1. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004; 306: 2090-3.
2. Babitt JL, Huang FW, Wrighting DM, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006; 38: 531-9.
3. Xia Y, Babitt JL, Sidis Y, et al. Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin. Blood. 2008; 111: 5195-204.
4. 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: 482-7.
5. 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: 4224-30.
6. Silvestri L, Pagani A, Camaschella C. Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. Blood. 2008; 111: 924-31.
7. Kuninger D, Kuns-Hashimoto R, Nili M, et al. Pro-protein convertases control the maturation and processing of the iron-regulatory protein. RGMc/hemojuvelin. BMC Biochem. 2008; 9: 9.
8. Lin L, Nemeth E, Goodnough JB, et al. Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site. Blood Cell Mol Dis. 2008; 40: 122-31.
9. Lin L, Goldberg YP, Ganz T. Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin. Blood. 2005; 106: 2884-9.
10. Nili M, Shinde U, Rotwein P. Soluble repulsive guidance molecule c/hemojuvelin is a broad spectrum bone morphogenetic protein (BMP) antagonist and inhibits both BMP2- and BMP6-mediated signaling and gene expression. J Biol Chem. 2010; 285: 24783-92.
11. 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.
12. Zhang AS, West AP Jr, Wyman AE, et al. Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells. J Biol Chem. 2005; 280: 33885-94.
13. 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: 4503-10.
14. Nili M, David L, Elferich J, et al. Proteomic analysis and molecular modelling characterize the iron-regulatory protein haemojuvelin/repulsive guidance molecule c. Biochem J. 2013; 452: 87-95.
15. Zhang AS, Yang F, Meyer K, et al. Neogenin-mediated hemojuvelin shedding occurs after hemojuvelin traffics to the plasma membrane. J Biol Chem. 2008; 283: 17494-502.
16. Kuninger D, Kuns-Hashimoto R, Kuzmickas R, et al. Complex biosynthesis of the muscle-enriched iron regulator RGMc. J Cell Sci. 2006; 119: 3273-83.
17. Frydlova J, Fujikura Y, Vokurka M, et al. Decreased hemojuvelin protein levels in mask mice lacking matriptase-2-dependent proteolytic activity. Physiol Res. 2013; 62: 405-11.
18. Kuns-Hashimoto R, Kuninger D, Nili M, et al. Selective binding of RGMc/hemojuvelin, a key protein in systemic iron metabolism, to BMP-2 and neogenin. Am J Physiol Cell Ph. 2008; 294: C994-1003.
19. Pagani A, Silvestri L, Nai A, et al. Hemojuvelin N-terminal mutants reach the plasma membrane but do not activate the hepcidin response. Haematologica. 2008; 93: 1466-72.
20. Finberg KE, Heeney MM, Campagna DR, et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet. 2008; 40: 569-71.
21. Silvestri L, Pagani A, Nai A, et al. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab. 2008; 8: 502-11.
22. Du X, She E, Gelbart T, et al. The serine protease TMPRSS6 is required to sense iron deficiency. Science. 2008; 320: 1088-92.
23. Folgueras AR, de Lara FM, Pendas AM, et al. Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood. 2008; 112: 2539-45.
24. Enns CA, Ahmed R, Zhang AS. Neogenin interacts with matriptase-2 to facilitate hemojuvelin cleavage. J Biol Chem. 2012; 287: 35104-17.
25. Maxson JE, Chen J, Enns CA, et al. Matriptase-2- and proprotein convertase-cleaved forms of hemojuvelin have different roles in the down-regulation of hepcidin expression. J Biol Chem. 2010; 285: 39021-8.
26. Silvestri L, Guillem F, Pagani A, et al. Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia. Blood. 2009; 113: 5605-8.
27. Silvestri L, Rausa M, Pagani A, et al. How to assess causality of TMPRSS6 mutations? Hum Mutat. 2013; 34: 1043-5.
28. Roy A, Kucukural A, Zhang Y. I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc. 2010; 5: 725-38.
29. Hess B, Kutzner C, Van Der Spoel D, et al. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput. 2008; 4: 435-47.
30. Bell CH, Healey E, van Erp S, et al. Structure of the repulsive guidance molecule (RGM)-neogenin signaling hub. Science. 2013; 341: 77-80.
31. Lanzara C, Roetto A, Daraio F, et al. Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis. Blood. 2004; 103: 4317-21.
32. Humpries W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graphics. 1996; 14: 33-8.