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

An-Sheng Zhang, Fan Yang, Jiaohong Wang, Hidekazu Tsukamoto, Caroline Enns

Research output: Contribution to journalArticle

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Abstract

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 were expressed in liver hepatocytes. Knockdown of neogenin decreased BMP4-induced hepcidin mRNA levels by 16-fold in HJV-expressing HepG2 cells but only by about 2-fold in cells transfected with either empty vector or G99V mutant HJV that does not bind BMPs. Further studies indicated that disruption of the HJV-neogenin interaction is responsible for a marked suppression of hepcidin expression. Moreover, in vivo studies showed that hepatic hepcidin mRNA could be significantly suppressed by blocking the interaction of HJV with full-length neogenin with a soluble fragment of neogenin in mice. Together, these results suggest that the HJV-neogenin interaction is required for the BMP-mediated induction of hepcidin expression when HJV is expressed. Combined with our previous studies, our results support that hepatic neogenin possesses two functions, mediation of cellular HJV release, and stimulation of HJV-enhanced hepcidin expression.

Original languageEnglish (US)
Pages (from-to)22580-22589
Number of pages10
JournalJournal of Biological Chemistry
Volume284
Issue number34
DOIs
StatePublished - Aug 21 2009

Fingerprint

Hepcidins
Bone
Bone and Bones
Proteins
Liver
Hepatocytes
GPI-Linked Proteins
neogenin
Messenger RNA
Hep G2 Cells
Transcription
Iron
Hormones

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Hemojuvelin-neogenin interaction is required for bone morphogenic protein-4-induced hepcidin expression. / Zhang, An-Sheng; Yang, Fan; Wang, Jiaohong; Tsukamoto, Hidekazu; Enns, Caroline.

In: Journal of Biological Chemistry, Vol. 284, No. 34, 21.08.2009, p. 22580-22589.

Research output: Contribution to journalArticle

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