Complex biosynthesis of the muscle-enriched iron regulator RGMc

David Kuninger, Robin Kuns-Hashimoto, Ryan Kuzmickas, Peter Rotwein

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The recently discovered repulsive guidance molecule c (RGMc or hemojuvelin) gene encodes a putative glycosylphosphatidylinositol (GPI)-anchored protein that is expressed in striated muscle and in liver. Mutations in this gene have been linked to the severe iron storage disease, juvenile hemochromatosis, although the mechanisms of action of RGMc in iron metabolism are unknown. As a first step toward understanding the molecular physiology of this protein, we studied its biosynthesis, processing and maturation. Production of RGMc occurs as an early and sustained event during skeletal muscle differentiation in culture and is secondary to RGMc gene activation. As assessed by pulse-chase studies and cell-surface labeling experiments, two classes of GPI-anchored and glycosylated RGMc molecules are targeted to the membrane and undergo distinct fates. Full-length RGMc is released from the cell surface and accumulates in extracellular fluid, where its half-life exceeds 24 hours. By contrast, the predominant membrane-associated isoform, a disulfide-linked heterodimer composed of N- and C-terminal fragments, is not found in the extracellular fluid, and is short-lived, as it disappears from the cell surface with a half-life of

Original languageEnglish (US)
Pages (from-to)3273-3283
Number of pages11
JournalJournal of Cell Science
Volume119
Issue number16
DOIs
StatePublished - Aug 15 2006

Fingerprint

Glycosylphosphatidylinositols
Iron
Extracellular Fluid
Muscles
Half-Life
Hemochromatosis
Membranes
Striated Muscle
Disulfides
Transcriptional Activation
Genes
Protein Isoforms
Skeletal Muscle
Proteins
Mutation
Liver
Type 2 Hemochromatosis

Keywords

  • Hemojuvelin
  • Juvenile hemochromatosis
  • Muscle
  • RGMc

ASJC Scopus subject areas

  • Cell Biology

Cite this

Kuninger, D., Kuns-Hashimoto, R., Kuzmickas, R., & Rotwein, P. (2006). Complex biosynthesis of the muscle-enriched iron regulator RGMc. Journal of Cell Science, 119(16), 3273-3283. https://doi.org/10.1242/jcs.03074

Complex biosynthesis of the muscle-enriched iron regulator RGMc. / Kuninger, David; Kuns-Hashimoto, Robin; Kuzmickas, Ryan; Rotwein, Peter.

In: Journal of Cell Science, Vol. 119, No. 16, 15.08.2006, p. 3273-3283.

Research output: Contribution to journalArticle

Kuninger, D, Kuns-Hashimoto, R, Kuzmickas, R & Rotwein, P 2006, 'Complex biosynthesis of the muscle-enriched iron regulator RGMc', Journal of Cell Science, vol. 119, no. 16, pp. 3273-3283. https://doi.org/10.1242/jcs.03074
Kuninger D, Kuns-Hashimoto R, Kuzmickas R, Rotwein P. Complex biosynthesis of the muscle-enriched iron regulator RGMc. Journal of Cell Science. 2006 Aug 15;119(16):3273-3283. https://doi.org/10.1242/jcs.03074
Kuninger, David ; Kuns-Hashimoto, Robin ; Kuzmickas, Ryan ; Rotwein, Peter. / Complex biosynthesis of the muscle-enriched iron regulator RGMc. In: Journal of Cell Science. 2006 ; Vol. 119, No. 16. pp. 3273-3283.
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