Submitted on January 12, 2003
Revised on May 21, 2003
Accepted on May 27, 2003
Molecular characterization of the first avian LDL receptor: role in sterol metabolism of ovarian follicular cells
Susanna Hummel, Edward G. Lynn, Andreas Osanger, Satoshi Hirayama, Johannes Nimpf, and Wolfgang J. Schneider
Molecular Genetics, Institute of Medical Biochemistry, University of Vienna, Vienna A - 1030
Corresponding Author: wjs{at}mol.univie.ac.at
ABSTRACT Low levels of expression and sluggish sterol-mediated regulation have been likely reasons for the failure to molecularly characterize a bona-fide LDL receptor in egg-laying species to date. The overall structure of the chicken LDL receptor, delineated here by cDNA cloning, has been conserved in evolution, since hallmark properties of mammalian LDL receptors are already present in the avian protein. The chicken receptor appears to prefer LDL over VLDL as ligand, in compliance with its main role in providing lipoprotein-derived cholesterol for steroid production in ovarian follicular cells. This is also compatible with the fact that estrogen administration increased hepatic LDL receptor expression in roosters despite dramatically stimulated VLDL production. In cultured chicken embryo fibroblasts, expression of the receptor was induced by incubation with cholesterol synthesis inhibitors such as a statin. Furthermore, preincubation of induced cells with a specific anti-receptor antibody blocks LDL endocytosis, demonstrating that the receptor is ligand-endocytosis competent. Finally, the distribution of LDL receptors among the extraoocytic cell populations lends support to a three-cell model for estrogen production within the ovarian follicle. In summary, the molecular characterization of the first avian LDL receptor reveals novel information about evolutionary, structural, and functional aspects of members of the supergene family of LDL receptor-related proteins.
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