Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK045598-02
Application #
3247083
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1992-09-30
Project End
1996-09-29
Budget Start
1993-09-30
Budget End
1994-09-29
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
American National Red Cross
Department
Type
DUNS #
003255213
City
Washington
State
DC
Country
United States
Zip Code
20006

  Publications

Ranganathan, S; Knaak, C; Morales, C R et al. (1999) Identification of low density lipoprotein receptor-related protein-2/megalin as an endocytic receptor for seminal vesicle secretory protein II. J Biol Chem 274:5557-63
Igdoura, S A; Argraves, W S; Morales, C R (1997) Low density lipoprotein receptor-related protein-1 expression in the testis: regulated expression in Sertoli cells. J Androl 18:400-10
Hammad, S M; Ranganathan, S; Loukinova, E et al. (1997) Interaction of apolipoprotein J-amyloid beta-peptide complex with low density lipoprotein receptor-related protein-2/megalin. A mechanism to prevent pathological accumulation of amyloid beta-peptide. J Biol Chem 272:18644-9
Morales, C R; Igdoura, S A; Wosu, U A et al. (1996) Low density lipoprotein receptor-related protein-2 expression in efferent duct and epididymal epithelia: evidence in rats for its in vivo role in endocytosis of apolipoprotein J/clusterin. Biol Reprod 55:676-83
Kounnas, M Z; Church, F C; Argraves, W S et al. (1996) Cellular internalization and degradation of antithrombin III-thrombin, heparin cofactor II-thrombin, and alpha 1-antitrypsin-trypsin complexes is mediated by the low density lipoprotein receptor-related protein. J Biol Chem 271:6523-9
Waegemann, K; Soll, J (1996) Phosphorylation of the transit sequence of chloroplast precursor proteins. J Biol Chem 271:6545-54
Stefansson, S; Lawrence, D A; Argraves, W S (1996) Plasminogen activator inhibitor-1 and vitronectin promote the cellular clearance of thrombin by low density lipoprotein receptor-related proteins 1 and 2. J Biol Chem 271:8215-20
Stefansson, S; Kounnas, M Z; Henkin, J et al. (1995) gp330 on type II pneumocytes mediates endocytosis leading to degradation of pro-urokinase, plasminogen activator inhibitor-1 and urokinase-plasminogen activator inhibitor-1 complex. J Cell Sci 108 ( Pt 6):2361-8
Godyna, S; Liau, G; Popa, I et al. (1995) Identification of the low density lipoprotein receptor-related protein (LRP) as an endocytic receptor for thrombospondin-1. J Cell Biol 129:1403-10
Kounnas, M Z; Loukinova, E B; Stefansson, S et al. (1995) Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin. J Biol Chem 270:13070-5

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