Nature Genetics
- 38, 531 - 539 (2006)
Published online: 9 April 2006; | doi:10.1038/ng1777
Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expressionJodie L Babitt1, Franklin W Huang2, 7, Diedra M Wrighting2, 7, Yin Xia1, 7, Yisrael Sidis3, 7, Tarek A Samad4, Jason A Campagna4, Raymond T Chung5, Alan L Schneyer3, Clifford J Woolf4, Nancy C Andrews2, 6 & Herbert Y Lin11
Program in Membrane Biology and Nephrology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. 2
Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. 3
Reproductive Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. 4
Neural Plasticity Research Group, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. 5
Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. 6
Howard Hughes Medical Institute, Boston, Massachusetts, USA. 7
These authors contributed equally to this work.
Correspondence should be addressed to Herbert Y Lin hlin@partners.org Hepcidin is a key regulator of systemic iron homeostasis. Hepcidin deficiency induces iron overload, whereas hepcidin excess induces anemia. Mutations in the gene encoding hemojuvelin (HFE2, also known as HJV) cause severe iron overload and correlate with low hepcidin levels, suggesting that hemojuvelin positively regulates hepcidin expression. Hemojuvelin is a member of the repulsive guidance molecule (RGM) family, which also includes the bone morphogenetic protein (BMP) coreceptors RGMA and DRAGON (RGMB). Here, we report that hemojuvelin is a BMP coreceptor and that hemojuvelin mutants associated with hemochromatosis have impaired BMP signaling ability. Furthermore, BMP upregulates hepatocyte hepcidin expression, a process enhanced by hemojuvelin and blunted in Hfe2-/- hepatocytes. Our data suggest a mechanism by which HFE2 mutations cause hemochromatosis: hemojuvelin dysfunction decreases BMP signaling, thereby lowering hepcidin expression.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
