Neogenin-mediated Hemojuvelin Shedding Occurs after Hemojuvelin Traffics to the Plasma Membrane

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Neogenin-mediated hemojuvelin shedding occurs after hemojuvelin traffics to the plasma membrane.

HFE2 (hemochromatosis type 2 gene) is highly expressed in skeletal muscle and liver hepatocytes. Its encoded protein, hemojuvelin (HJV), is a co-receptor for the bone morphogenetic proteins 2 and 4 (BMP2 and BMP4) and enhances the BMP-induced hepcidin expression. Hepcidin is a central iron regulatory hormone predominantly secreted from hepatocytes. HJV also binds neogenin, a membrane protein wi...

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Neogenin interacts with hemojuvelin through its two membrane-proximal fibronectin type III domains.

Hemojuvelin is a recently identified iron-regulatory protein that plays an important role in affecting the expression of hepcidin, a key iron regulatory hormone. Although the underlying mechanism of this process is not clear, several hemojuvelin-binding proteins, including the cell surface receptor neogenin and bone morphogenetic protein (BMP) cytokines, have been identified. The ectodomain of ...

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Defective targeting of hemojuvelin to plasma membrane is a common pathogenetic mechanism in juvenile hemochromatosis.

Hemojuvelin (HJV) positively modulates the iron regulator hepcidin, and its mutations are the major cause of juvenile hemochromatosis (JH), a recessive disease leading to iron overload. Defective HJV reduces hepcidin up-regulation both in humans and in Hjv-deficient mice. To investigate the JH pathogenesis and the functional properties of human HJV we studied the biosynthesis and maturation of ...

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Hemojuvelin N-terminal mutants reach the plasma membrane but do not activate the hepcidin response.

BACKGROUND Hemojuvelin is a glycosylphosphatidylinositol-anchored protein, expressed in liver, skeletal muscle and heart. As a co-receptor of bone morphogenetic protein, membrane hemojuvelin positively modulates the iron regulator hepcidin. Mutations of the gene encoding for hemojuvelin cause juvenile hemochromatosis, characterized by hepcidin deficiency and severe iron overload. We have previo...

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Hemojuvelin-neogenin interaction is required for bone morphogenic protein-4-induced hepcidin expression.

Hemojuvelin (HJV) is a glycosylphosphatidylinositol-linked protein and binds both bone morphogenic proteins (BMPs) and neogenin. Cellular HJV acts as a BMP co-receptor to enhance the transcription of hepcidin, a key iron regulatory hormone secreted predominantly by liver hepatocytes. In this study we characterized the role of neogenin in HJV-regulated hepcidin expression. Both HJV and neogenin ...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2008

ISSN: 0021-9258

DOI: 10.1074/jbc.m710527200