Opposing effects of apolipoproteins E and C on lipoprotein binding to low density lipoprotein receptor-related protein

Robert C. Kowal, Joachim Herz, Karl H. Weisgraber, Robert W. Mahley, Michael S. Brown, Joseph L. Goldstein

Research output: Contribution to journalArticlepeer-review

318 Scopus citations

Abstract

The low density lipoprotein receptor-related protein (LRP) from rat liver membranes binds apoprotein E (apoE)-enriched rabbit β-migrating very low density lipoproteins (β-VLDL) in a ligand blotting assay on nitrocellulose membranes. Binding was markedly activated when the β-VLDL was preincubated with recombinant human apoE-3, native human apoE-3 or E-4, or native rabbit apoE. Human apoE-2, which binds poorly (1-2% of apoE-3 binding) to low density lipoprotein receptors, was approximately 40% as effective as apoE-3 or apoE-4 in binding to LRP. Stimulation of apoE-dependent binding to LRP was blocked by the inclusion of a mixture of human apoC proteins, but not apoA-I or A-II, in the preincubation reaction. High concentrations of apoE did not overcome the apoC inhibition. The effects of apoE and apoC on the ligand blotting assay were paralleled by similar effects in the ability of β-VLDL to stimulate cholesteryl ester synthesis in mutant human fibroblasts that lack low density lipoprotein receptors. These properties of LRP are consistent with the known effects of apoE and apoC on uptake of chylomicron and very low density lipoprotein remnants in the liver and raise the possibility that LRP functions as a receptor for apoE-enriched forms of these lipoproteins in intact animals.

Original languageEnglish (US)
Pages (from-to)10771-10779
Number of pages9
JournalJournal of Biological Chemistry
Volume265
Issue number18
StatePublished - 1990

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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