The main goal of this project is to investigate the structure, function and pathogenic role of a large glycoprotein called gp 330. This molecule was first identified as a major pathogenic antigen in Heymann nephritis - a rat model of human membranous glomerulonephritis. In a later study, the primary structure of gp 330, as deduced from partial cDNAs, was found to have considerable homology to the low density lipoprotein (LDL) receptor and the LDL receptor related protein (LRP), also known as the alpha2 macroglobulin receptor (alpha2MR). Recently, it has been shown that several known ligands of LRP/alpha2 MR bind to gp 330 in vitro, but the physiologic relevance of these observations is unknown, since gp 330 and LRP/alpha2MR have quite different distributions in vivo. Gp 330 is largely restricted to a group of epithelial cells whose major function appears to be absorption. A 39-44 KD protein invariably co-purifies with gp 330 and LRP/alpha2MR; this receptor associated protein (alpha2MRAP) inhibits the binding of ligands to gp 330 or LRP/alpha2MR in vitro, but its role in vivo is unknown. Major goals of this project are to obtain a full length cDNA encoding gp 330, investigate its receptor function in vivo, and to clarify the function of alpha2MRAP. In addition, the role of alpha2MRAP, gp 330 and ligands of gp 330 in the development of immune deposits in Heymann nephritis will be studied. The research may provide information about the receptor function of gp 330 and its role in specialized epithelial cells. The studies on Heymann nephritis should reveal new information about how immune deposits form in glomeruli, which is an important mechanism in major forms of human glomerulonephritis.
Showing the most recent 10 out of 11 publications
