Date

April 2011

Document Type

Dissertation

Degree Name

Ph.D.

Department

Dept. of Cell and Developmental Biology

Institution

Oregon Health & Science University

Abstract

Mutations in hemojuvelin (HJV) lead to the iron overload disorder juvenile hemochromatosis. HJV regulates iron metabolism by activating transcription of the iron regulatory peptide, hepcidin, through the bone morphogenetic protein (BMP) signaling pathway. HJV is proposed to act as a co-receptor for BMP ligands, but the exact mechanism by which it potentiates BMP signaling is not clear. To better understand the role of HJV in the regulation of iron metabolism, I analyzed its trafficking and processing. HJV traffics to the cell surface while avoiding modification by glycosylases and proteases that reside in the Golgi. After reaching the cell surface, HJV undergoes retrograde trafficking to the Golgi, where it is further modified and cleaved by furin. HJV is cleaved by the furin family of proprotein convertases, which generates a soluble form of HJV that antagonizes BMP signaling. Reaching the cell surface prior to cleavage and secretion may allow HJV to participate in BMP signaling at th

Identifier

doi:10.6083/M4T43R2S

School

School of Medicine

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