Self-assembly of HEK cell-secreted ApoE particles resembles ApoE enrichment of lipoproteins as a ligand for the LDL receptor-related protein

Mary Jo Ladu, W. Blaine Stine, Masaaki Narita, Godfrey S. Getz, Catherine A. Reardon, Guojun Bu

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Recent studies have shown that the lipidation and assembly state of apolipoprotein E (apoE) determine receptor recognition and amyloid-β peptide (Aβ) binding. We previously demonstrated that apoE secreted by HEK cells stably expressing apoE3 or apoE4 (HEK-apoE) binds Aβ and inhibits Aβ-induced neurotoxicity by an isoform-specific process that requires apoE receptors. Here we characterized the structure of HEK-apoE assemblies and determined their receptor binding specificity. By chromatography, HEK-apoE elutes in high molecular mass fractions and is the size of plasma HDL, consistent with a multiprotein assembly. No lipid was associated with these apoE assemblies. Several methods for analyzing receptor binding indicate that HEK-apoE is a ligand for low-density lipoprotein (LDL) receptor-related protein (LRP) but not the LDL receptor. This suggests that self-assembly of apoE may induce a functional conformation necessary for binding to LRP. Our results indicate that, in addition to lipid content, the assembly state of apoE influences Aβ binding and receptor recognition.

Original languageEnglish (US)
Pages (from-to)381-390
Number of pages10
JournalBiochemistry
Volume45
Issue number2
DOIs
StatePublished - Jan 17 2006

ASJC Scopus subject areas

  • Biochemistry

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