Processing of hemojuvelin requires retrograde trafficking to the Golgi in HepG2 cells

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Abstract

Hemojuvelin (HJV) was recently identified as a critical regulator of iron ho-meostasis. It is either associated with cell membranes through a glycosylphosphati-dylinositol anchor or released as a soluble form. Membrane-anchored HJV acts as a coreceptor for bone morphogenetic proteins and activates the transcription of hepcidin, a hormone that regulates iron efflux from cells. Soluble HJV antagonizes bone morphogenetic protein signaling and suppresses hepcidin expression. In this study, we examined the trafficking and processing of HJV. Cellular HJV reached the plasma membrane without obtaining complex oligosaccharides, indicating that HJV avoided Golgi processing. Secreted HJV, in contrast, has complex oligosaccharides and can be derived from HJV with high-mannose oligosac-charides at the plasma membrane. Our results support a model in which retrograde trafficking of HJV before cleavage is the predominant processing pathway. Release of HJV requires it to bind to the transmembrane receptor neogenin. Neo-genin does not, however, play a role in HJV trafficking to the cell surface, suggesting that it could be involved either in retrograde trafficking of HJV or in cleavage leading to HJV release.

Original languageEnglish (US)
Pages (from-to)1786-1793
Number of pages8
JournalBlood
Volume113
Issue number8
DOIs
StatePublished - Feb 19 2009

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Hep G2 Cells
Cell membranes
Hepcidins
Bone Morphogenetic Proteins
Cell Membrane
Oligosaccharides
Iron
Processing
Transcription
Mannose
Anchors
Hormones
Membranes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Processing of hemojuvelin requires retrograde trafficking to the Golgi in HepG2 cells. / Maxson, Julia; Enns, Caroline; Zhang, An-Sheng.

In: Blood, Vol. 113, No. 8, 19.02.2009, p. 1786-1793.

Research output: Contribution to journalArticle

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