Neogenin Interacts with Matriptase-2 to Facilitate Hemojuvelin Cleavage

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

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Matriptase-2, a membrane protein encoded by the Tmprss6 gene, is a negative regulator of hepcidin expression. Although matriptase-2 has been proposed to cleave membrane hemojuvelin, we have recently found decreased hemojuvelin protein levels in Tmprss6 -/- mice. The purpose of this study was to confirm this observation by determining hemojuvelin protein levels in another strain of mice with dis...

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Hemojuvelin (HJV), the coreceptor of the BMP-SMAD pathway that up-regulates hepcidin transcription, is a repulsive guidance molecule (RGMc) which undergoes a complex intracellular processing. Following autoproteolysis, it is exported to the cell surface both as a full-length and a heterodimeric protein. In vitro membrane HJV (m-HJV) is cleaved by the transmembrane serine protease TMPRSS6 to att...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2012

ISSN: 0021-9258

DOI: 10.1074/jbc.m112.363937