Low density lipoprotein receptor-related protein mediates uptake of cholesteryl esters derived from apoprotein E-enriched lipoproteins

R. C. Kowal, J. Herz, J. L. Goldstein, V. Esser, M. S. Brown

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Abstract

Low density lipoprotein receptor-related protein (LRP) is a recently described cell-surface protein of 4544 amino acids that contains reiterated sequences found in the 839-amino acid receptor for low density lipoprotein (LDL). In the current studies, we purified LRP from rat liver, prepared polyclonal antibodies that recognize the extracellular domain, and demonstrated as immunoreactive protein of ~ 600 kDa in human fibroblasts. The function of this LRP was studied in mutant human fibroblasts that do not produce LDL receptors. The mutant cells were incubated with β-migrating very low density lipoprotein (β-VLDL) that was isolated from cholesterol-fed rabbits and artificially enriched with apoprotein (apo) E by incubation in vitro with human apo E produced in a bacterial expression system. The apo E-enriched β-VLDL, but not unincubated β-VLDL, stimulated incorporation of [14C]oleate into cholesteryl [14C]oleate 20- to 40-fold in the mutant cells. This stimulation was blocked by chloroquine, suggesting that such stimulation resulted from receptor-mediated uptake and lysosomal hydrolysis of the cholesteryl esters in apo E-enriched β-VLDL. Stimulation of cholesterol esterification was blocked by the antibody against LRP, but not by an antibody against the LDL receptor. Unlike the LDL receptor, the amount of LRP was not reduced when cells were incubated with oxygenated sterols. We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E.

Original languageEnglish (US)
Pages (from-to)5810-5814
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number15
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • General

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