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Cleavage of HJV is independent of its GPI‐anchor
Author(s) -
Maxson Julia Elizabeth,
Zhang AnSheng,
Enns Caroline
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.683.6
Subject(s) - furin , hepcidin , microbiology and biotechnology , secretion , chemistry , bone morphogenetic protein , ectodomain , cleavage (geology) , proprotein convertases , biology , receptor , biochemistry , ldl receptor , gene , immunology , paleontology , fracture (geology) , inflammation , enzyme , lipoprotein , cholesterol
Mutations in hemojuvelin (HJV) lead to the iron overload disorder juvenile hemochromatosis. HJV is a GPI‐linked protein that increases expression of the iron regulatory peptide hormone, hepcidin. Hepcidin negatively regulates iron uptake from the intestine. GPI‐linked HJV potentiates bone morphogenetic protein (BMP) signaling to upregulate hepcidin expression. HJV can also be cleaved by the proteases furin and matriptase‐2, releasing it from its GPI‐anchor and allowing it to be secreted from cells. In contrast to GPI‐linked HJV, secreted HJV negatively regulates BMP signaling and decreases hepcidin expression. To investigate the role of the GPI‐anchor in cleavage and secretion of HJV, we created chimeric proteins with the ectodomain of HJV and the transmembrane and cytoplasmic domains of either low‐density lipoprotein receptor (LDLR) or furin in lieu of the GPI‐anchor. These chimeric proteins appear to traffic similarly to GPI‐HJV, and are cleaved by furin and secreted from cells. Truncated forms of HJV that have neither a transmembrane or GPI‐anchor, are also cleaved by furin and are secreted from cells, but appear to have different kinetics of post‐translational processing than membrane anchored HJV. These studies indicate that the GPI‐anchor is not required for cleavage and secretion of HJV. This work is funded by NIH‐DK080765.