Journal of Biological Chemistry
Volume 278, Issue 16, 18 April 2003, Pages 14370-14378
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LIPIDS AND LIPOPROTEINS
Recycling of Apoprotein E Is Associated with Cholesterol Efflux and High Density Lipoprotein Internalization*

https://doi.org/10.1074/jbc.M209006200Get rights and content
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After receptor-mediated endocytosis of triglyceride-rich lipoproteins (TRL) into the liver, TRL particles are immediately disintegrated in peripheral endosomal compartments. Whereas core lipids and apoprotein B are delivered for degradation into lysosomes, TRL-derived apoE is efficiently recycled back to the plasma membrane. This is followed by apoE re-secretion and association of apoE with high density lipoproteins (HDL). Because HDL and apoE can independently promote cholesterol efflux, we investigated whether recycling of TRL-derived apoE in human hepatoma cells and fibroblasts could be linked to intracellular cholesterol transport. In this study we demonstrate that HDL3 does not only act as an extracellular acceptor for recycled apoE but also stimulates the recycling of internalized TRL-derived apoE. Furthermore, radioactive pulse-chase experiments indicate that apoE recycling is accompanied by cholesterol efflux. Confocal imaging reveals co-localization of apoE and cholesterol in early endosome antigen 1-positive endosomes. During apoE re-secretion, HDL3-derived apoA-I is found in these early endosome antigen 1, cholesterol-containing endosomes. As shown by time-lapse fluorescence microscopy, apoE recycling involves the intracellular trafficking of apoA-I to pre-existing and TRL-derived apoE/cholesterol-containing endosomes in the periphery. Thus, these studies provide evidence for a new intracellular link between TRL-derived apoE, cellular cholesterol transport, and HDL metabolism.

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Published, JBC Papers in Press, February 12, 2003, DOI 10.1074/jbc.M209006200

*

This work was supported in part by the Deutsche Forschungsgemeinschaft Grants Be 829/5-1, Ja 421/3-1, and Ri 436/8-1 and Ministerio de Ciencia y Tecnologia Grants PM99-0166, Acciones Integradas HA98-0007, and Generalitat de Catalunya BE2002 (to C. E.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a fellowship from the Studienstiftung des Deutschen Volkes.

Recipient of Fellowship GRK 336 from the Deutsche Forschungsgemeinschaft-financed Graduiertenkolleg.