Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression

@article{Babitt2006BoneMP,
  title={Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression},
  author={Jodie L Babitt and Franklin W. Huang and Diedra M. Wrighting and Yin Xia and Yisrael Sidis and Tarek A. Samad and Jason A. Campagna and Raymond T. Chung and Alan L. Schneyer and Clifford J. Woolf and Nancy C. Andrews and Herbert Y. Lin},
  journal={Nature Genetics},
  year={2006},
  volume={38},
  pages={531-539}
}
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… 
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TLDR
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TLDR
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TLDR
Dietary iron sensing and inflammatory pathways converge in the regulation of the key regulator hepcidin, but how these two pathways intersect remains unclear.
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TLDR
This review highlights recent work uncovering the mechanism of action of HJV and the BMP-SMAD signaling pathway in regulating hepcidin expression in the liver, as well as additional studies investigating possible extra-hepatic functions of HJC.
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TLDR
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TLDR
It is demonstrated that one type I BMP receptor, Alk3, is critically responsible for basal hepcidin expression, whereas 2 type II BMP receptors, AlK2 and AlK3, are required for regulation of hePCidin gene expression in response to iron and BMP signaling.
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TLDR
Impaired BMP signaling underlies the hepcidin deficiency of HFE‐HH, and the inhibitory Smads, Smad6, and Smad7 are identified as potential disruptors of this signal and, hence, contributors to the pathogenesis of this disease.
Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis.
TLDR
Evidence is provided that neogenin plays a critical role in iron homeostasis by regulation of HJV secretion and bone morphogenetic protein (BMP) signaling, and studies demonstrate thatNeogenin may stabilize HJV, a glycosylphosphatidylinositol-anchored protein that interacts with neogenIn and suppresses its secretion.
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