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 Bu, Alan L. Schwartz

Producción científica: Articlerevisión exhaustiva

41 Citas (Scopus)


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.

Idioma originalEnglish (US)
Páginas (desde-hasta)743-749
Número de páginas7
PublicaciónJournal of Biochemistry
EstadoPublished - nov 1 2002
Publicado de forma externa

ASJC Scopus subject areas

  • General Medicine


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