STRUCTURE AND FUNCTION OF GP330

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The low density lipoprotein receptor (LDLR) is at the head of an emerging family of structurally and perhaps functionally related receptors. The family presently contains five members that include the LDLR, alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha2MR/LRP), the 95 kDa avian oocyte-specific receptor for the yolk precursor vitellogenin, the avian 380 kDa ovarian follicle membrane protein, and the kidney proximal tubule membrane protein, glycoprotein 330 (gp330). Although gp330 has been implicated as the pathogenic antigen for Heymann nephritis, the rat model for membranous glomerulonephropathy, and it has been localized to coated-pits of kidney brush border epithelial cells, its function is not known. The emphasis of this proposal is on determining the structure and biological function of gp330. The objectives are to (a) determine the complete amino acid sequence of human gp330 by cDNA cloning, (b) to characterize the functional properties of gp330 by identifying its ligand(s) particularly in the context of renal epithelium where gp330 is highly expressed and, (c) to determine the expression pattern of gp330 in adult and embryonic tissues as well as in cultured cell lines. A related aim of this project is to isolate and characterize new members of the LDLR family using homology-PCR cloning and degenerate oligonucleotide screening of genomic libraries.