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J. Biol. Chem., Vol. 278, Issue 16, 14370-14378, April 18, 2003
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From the 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.
Recycling of Apoprotein E Is Associated with
Cholesterol Efflux and High Density Lipoprotein Internalization*
§,,¶,
,, and
Institute for Medical Biochemistry and
Molecular Biology, the Department of Molecular Cell Biology and the
** Department of Internal Medicine, University Hospital
Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany and
Departament de Biologia Cellular, Institut
d'Investigacions Biomèdiques August Pi i Sunyer, Facultat de
Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
*
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 Fellowship GRK 336 from the Deutsche
Forschungsgemeinschaft-financed Graduiertenkolleg.
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