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Functional expression of low density lipoprotein receptor- related protein is controlled by receptor-associated protein in vivo

Item Type:Article
Title:Functional expression of low density lipoprotein receptor- related protein is controlled by receptor-associated protein in vivo
Creators Name:Willnow, T.E. and Armstrong, S.A. and Hammer, R.E. and Herz, J.
Abstract:The 39-kDa receptor-associated protein (RAP) associates with the multifunctional low density lipoprotein (LDL) receptor-related protein (LRP) and thereby prevents the binding of all known ligands, including alpha 2-macroglobulin and chylomicron remnants. RAP is predominantly localized in the endoplasmic reticulum, raising the possibility that it functions as a chaperone or escort protein in the biosynthesis or intracellular transport of LRP. Here we have used gene targeting to show that RAP promotes the expression of functional LRP in vivo. The amount of mature, processed LRP is reduced in liver and brain of RAP-deficient mice. As a result, hepatic clearance of alpha 2-macroglobulin is impaired and remnant lipoproteins accumulate in the plasma of RAP-deficient mice that also lack functional LDL receptors. These results are consistent with the hypothesis that RAP stabilizes LRP within the secretory pathway. They also suggest a further mechanism by which the activity of an endocytic receptor may be modulated in vivo.
Keywords:Apolipoproteins, Asialoglycoproteins, Base Sequence, Brain, Carrier Proteins, Cholesterol, Genetic Crosses, Endocytosis, Endoplasmic Reticulum, Genomic Library, Glycoproteins, Immunoblotting, LDL-Receptor Related Protein 1, LDL-Receptor Related Protein-Associated Protein, Liver, Membrane Proteins, Inbred C57BL Mice, Inbred Strains Mice, Mutant Strains Mice, Molecular Sequence Data, Insertional Mutagenesis, Oligodeoxyribonucleotides, Immunologic Receptors, LDL Receptors, Nucleic Acid Sequence Homology, Triglycerides, alpha-Fetoproteins, alpha-Macroglobulins, Animals, Mice, Cattle
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:92
Number:10
Page Range:4537-4541
Date:9 May 1995
Official Publication:http://www.pnas.org/cgi/content/abstract/92/10/4537
PubMed:View item in PubMed

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