Ferroportin diseases: Functional studies, a link between genetic and clinical phenotype

Human Mutation

Volumn 34, Issue 11, 2013, Pages 1529-1536

  Détivaud, Lénaïck ^a,b   Island, Marie Laure ^a,b   Jouanolle, Anne Marie ^a   Ropert, Martine ^a,b   Bardou Jacquet, Edouard ^a,b,c   Le Lan, Caroline ^a,b   Mosser, Annick ^a   Leroyer, Patricia ^b,c   Deugnier, Yves ^a,b,c   David, Véronique ^a,c   Brissot, Pierre ^a,b,c   Loréal, Olivier ^a,b,c  

^a RENNES UNIVERSITY HOSPITAL   (France)

^b Univ Rennes   (France)

^c UNIVERSITÉ DE RENNES 1   (France)

Author keywords

Ferroportin; Hemochromatosis; Hepcidin; Iron overload; SLC40A1

Indexed keywords

FERROPORTIN; HEPCIDIN;

ARTICLE; CONTROLLED STUDY; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; INDUCED MUTATION; IRON OVERLOAD; LOSS OF FUNCTION MUTATION; PHENOTYPE; PRIORITY JOURNAL; PROTEIN LOCALIZATION;

FERROPORTIN; HEMOCHROMATOSIS; HEPCIDIN; IRON OVERLOAD; SLC40A1;

CATION TRANSPORT PROTEINS; FERRITINS; GENE EXPRESSION; GENETIC ASSOCIATION STUDIES; HEK293 CELLS; HUMANS; INTRACELLULAR SPACE; IRON; IRON OVERLOAD; LIVER; MUTATION; TRANSFERRIN;

EID: 84885433847     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.22396     Document Type: Article

References (34)

1. Abboud S, Haile DJ. 2000. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem 275:19906-19912.
2. Bach V, Remacha A, Altés A, Barceló MJ, Molina MA, Baiget M. 2006. Autosomal dominant hereditary hemochromatosis associated with two novel ferroportin 1 mutations in Spain. Blood Cells Mol Dis 36:41-45.
3. Barisani D, Pelucchi S, Mariani R, Galimberti S, Trombini P, Fumagalli D, Meneveri R, Nemeth E, Ganz T, Piperno A. 2008. Hepcidin and iron-related gene expression in subjects with Dysmetabolic Hepatic Iron Overload. J Hepatol 49:123-133.
4. Brissot P, Bardou-Jacquet E, Jouanolle AM, Loréal O. 2011. Iron disorders of genetic origin: a changing world. Trends Mol Med 17:707-713.
5. Cunat S, Giansily-Blaizot M, Bismuth M, Blanc F, Dereure O, Larrey D, Quellec AL, Pouderoux P, Rose C, Raingeard I, Renard E, Schved JF, et al. 2007. Global sequencing approach for characterizing the molecular background of hereditary iron disorders. Clin Chem 53:2060-2069.
6. De Domenico I, Vaughn MB, Li L, Bagley D, Musci G, Ward DM, Kaplan J. 2006. Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome. EMBO J 25:5396-5404.
7. De Domenico I, Ward DM, Langelier C, Vaughn MB, Nemeth E, Sundquist WI, Ganz T, Musci G, Kaplan J. 2007. The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol Biol Cell 18:2569-2578.
8. Détivaud L, Nemeth E, Boudjema K, Turlin B, Troadec MB, Leroyer P, Ropert M, Jacquelinet S, Courselaud B, Ganz T, Brissot P, Loréal O. 2005. Hepcidin levels in humans are correlated with hepatic iron stores, hemoglobin levels, and hepatic function. Blood 106:746-748.
9. Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, Moynihan J, Paw BH, Drejer A, Barut B, Zapata A, Law TC, Brugnara C, et al. 2000. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 403:776-781.
10. Drakesmith H, Schimanski LM, Ormerod E, Merryweather-Clarke AT, Viprakasit V, Edwards JP, Sweetland E, Bastin JM, Cowley D, Chinthammitr Y, Robson KJ, Townsend AR. 2005. Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin. Blood 106:1092-1097.
11. Evstatiev V, Gasche V. 2012. Iron sensing and signaling. Gut 61:933-952.
12. Krause A, Neitz S, Mägert HJ, Schulz A, Forssmann WG, Schulz-Knappe P, Adermann K. 2000. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett 480:147-150.
13. Le Lan C, Mosser A, Ropert M, Detivaud L, Loustaud-Ratti V, Vital-Durand D, Roget L, Bardou-Jacquet E, Turlin B, David V, Loréal O, Deugnier Y, et al. 2011. Sex and acquired co-factors determine phenotypes of ferroportin disease. Gastroenterology 140:1199-1207.
14. Liu XB, Yang F, Haile DJ. 2005. Functional consequences of ferroportin 1 mutations. Blood Cells Mol Dis 35:33-46.
15. Mayr R, Griffiths WJ, Hermann M, McFarlane I, Halsall DJ, Finkenstedt A, Douds A, Davies SE, Janecke AR, Vogel W, Cox TM, Zoller H. 2011. Identification of mutations in SLC40A1 that affect ferroportin function and phenotype of human ferroportin iron overload. Gastroenterology 140:2056-2063.
16. Mayr R, Janeck AR, Schranz M, Griffiths WJ, Vogel W, Pietrangelo A, Zoller H. 2010. Ferroportin disease: a systematic meta-analysis of clinical and molecular findings. J Hepatol 53:941-949.
17. McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, Barrow D, Miret S, Bomford A, Peters TJ, Farzaneh F, Hediger MA, Hentze MW, et al. 2000. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 5:299-309.
18. Montosi G, Donovan A, Totaro A, Garuti C, Pignatti E, Cassanelli S, Trenor CC, Gasparini P, Andrews NC, Pietrangelo A. 2001. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest 108:619-623.
19. Morris TJ, Litvinova MM, Ralston D, Mattman A, Holmes D, Lockitch G. 2005. A novel ferroportin mutation in a Canadian family with autosomal dominant hemochromatosis. Blood Cells Mol Dis 35:309-314.
20. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J. 2004. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090-2093.
21. Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, Vaulont S. 2001. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci USA 98:8780-8785.
22. Njajou OT, Vaessen N, Joosse M, Berghuis B, van Dongen JW, Breuning MH, Snijders PJ, Rutten WP, Sandkuijl LA, Oostra BA, van Duijn CM, Heutink P. 2001. A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis. Nat Genet 28:213-214.
23. Ohtake T, Saito H, Hosoki Y, Inoue M, Miyoshi S, Suzuki Y, Fujimoto Y, Kohgo Y. 2007. Hepcidin is down-regulated in alcohol loading. Alcohol Clin Exp Res 31:S2-S8.
24. Pantopoulos K. 2004. Iron metabolism and the IRE/IRP regulatory system: an update. Ann N Y Acad Sci 101:1-13.
25. Park CH, Valore EV, Waring AJ, Ganz T. 2001. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276:7806-7810.
26. Pelucchi S, Mariani R, Salvioni A, Bonfadini S, Riva A, Bertola F, Trombini P, Piperno A. 2008. Novel mutations of the ferroportin gene (SLC40A1): analysis of 56 consecutive patients with unexplained iron overload. Clin Genet 73:171-178.
27. Pietrangelo A, Caleffi A, Corradini E. 2011. Non-HFE hepatic iron overload. Semin Liver Dis 31:302-318.
28. Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loréal O. 2001. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 276:7811-7819.
29. Rice AE, Mendez MJ, Hokanson CA, Rees DC, Björkman PJ. 2009. Investigation of the biophysical and cell biological properties of ferroportin, a multipass integral membrane protein iron exporter. J Mol Biol 386:717-732.
30. Ruivard M, Lainé F, Ganz T, Olbina G, Westerman M, Nemeth E, Rambeau M, Mazur A, Gerbaud L, Tournilhac V, Abergel A, Philippe P et al. 2009. Iron absorption in dysmetabolic iron overload syndrome is decreased and correlates with increased plasma hepcidin. J Hepatol 50:1219-1225.
31. Santos PC, Cançad RD, Pereira AC, Schettert IT, Soares RA, Pagliusi RA, Hirata RD, Hirata MH, Teixeira AC, Figueiredo MS, Chiattone CS, Krieger JE, et al. 2011. Hereditary hemochromatosis: mutations in genes involved in iron homeostasis in Brazilian patients. Blood Cells Mol Dis 46:302-307.
32. Schimanski LM, Drakesmith H, Merryweather-Clarke AT, Viprakasit V, Edwards JP, Sweetland E, Bastin JM, Cowley D, Chinthammitr Y, Robson KJ, Townsend AR. 2005. In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations. Blood 105:4096-4102.
33. Schneider CA, Rasband WS, Eliceiri KW. 2012. NIH Image to ImageJ: 25 years of image analysis. Nature Methods 9:671-675.
34. Wallace DF, Harris JM, Subramaniam VN. 2010. Functional analysis and theoretical modeling of ferroportin reveals clustering of mutations according to phenotype. Am J Physiol Cell Physiol 298:75-84.