The recycling of apolipoprotein E and its amino-terminal 22 kDa fragment: evidence for multiple redundant pathways.

Farkas MH, Weisgraber KH, Shepherd VL, Linton MF, Fazio S, Swift LL
J Lipid Res. 2004 45 (8): 1546-54

PMID: 15145976 · DOI:10.1194/jlr.M400104-JLR200

A portion of apolipoprotein E (apoE) internalized by hepatocytes is spared degradation and is recycled. To investigate the intracellular routing of recycling apoE, primary hepatocyte cultures from LDL receptor-deficient mice and mice deficient in receptor-associated protein [a model of depressed expression of LDL receptor-related protein (LRP)] were incubated with human VLDL containing 125I-labeled human recombinant apoE3. Approximately 30% of the internalized intact apoE was recycled after 4 h. The N-terminal 22 kDa fragment of apoE was also resecreted, demonstrating that this apoE domain contains sufficient sequence to recycle. The 22 kDa fragment has reduced affinity for lipoproteins, suggesting that apoE recycling is linked to the ability of apoE to bind directly to a recycling receptor. Finally, apoE was found to recycle equally well in the presence of brefeldin A, a drug that blocks transport from the endoplasmic reticulum and leads to collapse of the Golgi stacks. Our studies demonstrate that apoE recycling occurs 1) in the absence of the LDL receptor or under conditions of markedly reduced LRP expression; 2) when apoE lacks the carboxyl-terminal domain, which allows binding to the lipoprotein; and 3) in the absence of an intact Golgi apparatus. We conclude that apoE recycling occurs through multiple redundant pathways.

Copyright 2004 American Society for Biochemistry and Molecular Biology, Inc.

MeSH Terms (10)

Animals Apolipoproteins E Brefeldin A Cholesterol, VLDL Electrophoresis, Polyacrylamide Gel Hepatocytes Humans Mice Mice, Inbred ICR Protein Synthesis Inhibitors

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