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

T. E. Willnow, S. A. Armstrong, Robert E Hammer, Joachim Herz

Research output: Contribution to journalArticle

238 Scopus citations

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 α2- 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 α2-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.

Original languageEnglish (US)
Pages (from-to)4537-4541
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number10
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • General

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