Cellular catabolism of lipid poor apolipoprotein E via cell surface LDL receptor-related protein

Masaaki Narita, David M. Holtzman, Anne M. Fagan, Mary Jo LaDu, Li Yu, Xianlin Han, Richard W. Gross, Guojun D Bu, Alan L. Schwartz

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Apolipoprotein E (apoE), an apoprotein involved in lipid transport in both the plasma and within the brain, mediates the binding of lipoproteins to members of the low density lipoprotein (LDL) receptor family including the LDL receptor and the LDL receptor-related protein (LRP). ApoE/LRP interactions may be particularly important in brain where both are expressed at high levels, and polymorphisms in the apoE and LRP genes have been linked to AD. To date, only apoE-enriched lipoproteins have been shown to be LRP ligands. To investigate further whether other, more lipid-poor forms of apoE interact with LRP, we tested whether lipid-free apoE in the absence of lipoprotein particles interacts with its cell-surface receptors. No detectable lipid was found associated with bacterially expressed and purified apoE either prior to or following incubation with cells when analyzed by electrospray ionization mass spectrometry. We found that the degradation of lipid-poor 125I-apoE was significantly higher in wild type as compared to LRP-deficient cells, and was inhibited by receptor-associated protein (RAP). In contrast, 125I-apoE-enriched β-VLDL was degraded by both LRP and the LDL receptor. When analyzed via a single cycle of endocytosis, 125I-apoE was internalized prior to its subsequent intracellular degradation with kinetics typical of receptor-mediated endocytosis. Thus, we conclude that a very lipid-poor form of apoE can be catabolized via cell surface LRP, suggesting that the conformation of apoE necessary for recognition by LRP can be imposed by situations other than an apoE-enriched lioprotein.

Original languageEnglish (US)
Pages (from-to)743-749
Number of pages7
JournalJournal of Biochemistry
Volume132
Issue number5
StatePublished - Nov 1 2002
Externally publishedYes

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Keywords

  • ApoE
  • Endocytosis
  • LRP
  • Neuron
  • Receptor

ASJC Scopus subject areas

  • Biochemistry

Cite this

Narita, M., Holtzman, D. M., Fagan, A. M., LaDu, M. J., Yu, L., Han, X., Gross, R. W., Bu, G. D., & Schwartz, A. L. (2002). Cellular catabolism of lipid poor apolipoprotein E via cell surface LDL receptor-related protein. Journal of Biochemistry, 132(5), 743-749.