RGMc (Repulsive Guidance Molecule c), or hemojuvelin, has been genetically linked with the iron overloading disorder juvenile hemochromatosis. Patients with juvenile hemochromatosis and RGMc knockout mice exhibit iron overloading in the liver, heart, and pancreas, and have decreased hepatic expression of the key iron regulatory protein, hepcidin. These observations suggest that RGMc plays a critical role in the regulation of systemic iron homeostasis, although its mechanisms of action are unknown. Initial studies have shown that RGMc binds to the transmembrane protein neogenin. The focus of this application is to test the hypothesis that neogenin functions as a receptor for RGMc. The following Specific Aims are proposed to test this hypothesis: 1. to define the nature of the interaction between RGMc and neogenin, 2; to determine whether neogenin mediates the biological actions of RGMc. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK076348-02
Application #
7274730
Study Section
Special Emphasis Panel (ZRG1-F10-H (20))
Program Officer
Podskalny, Judith M,
Project Start
2006-08-01
Project End
2007-10-04
Budget Start
2007-08-01
Budget End
2007-10-04
Support Year
2
Fiscal Year
2007
Total Cost
$10,959
Indirect Cost
Name
Oregon Health and Science University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Kuns-Hashimoto, Robin; Kuninger, David; Nili, Mahta et al. (2008) Selective binding of RGMc/hemojuvelin, a key protein in systemic iron metabolism, to BMP-2 and neogenin. Am J Physiol Cell Physiol 294:C994-C1003
Kuninger, David; Kuns-Hashimoto, Robin; Nili, Mahta et al. (2008) Pro-protein convertases control the maturation and processing of the iron-regulatory protein, RGMc/hemojuvelin. BMC Biochem 9:9