Recycling of apolipoprotein E and lipoprotein lipase through endosomal compartments in vivo.
We have recently described a novel recycling pathway of triglyceride-rich lipoprotein (TRL)-associated apolipoprotein (apo) E in human hepatoma cells. We now demonstrate that not only TRL-derived apoE but also lipoprotein lipase (LPL) is efficiently recycled in vitro and in vivo. Similar recycling kinetics of apoE and LPL in normal and low density lipoprotein receptor-negative human fibroblasts also indicate that the low density lipoprotein receptor-related protein seems to be involved. Intracellular sorting mechanisms are responsible for reduced lysosomal degradation of both ligands after receptor-mediated internalization. Immediately after internalization in rat liver, TRLs are disintegrated, and apoE and LPL are found in endosomal compartments, whereas TRL-derived phospholipids accumulate in the perinuclear region of hepatocytes. Subsequently, substantial amounts of both proteins can be found in purified recycling endosomes, indicating a potential resecretion of these TRL components. Pulse-chase experiments of perfused rat livers with radiolabeled TRLs demonstrated a serum-induced release of internalized apoE and LPL into the perfusate. Analysis of the secreted proteins identified approximately 80% of the recycled TRL-derived proteins in the high density lipoprotein fractions. These results provide the first evidence that recycling of TRL-derived apoE and LPL could play an important role in the modulation of lipoproteins in vivo.
Heeren
J
J
Department of Medical Biochemistry and Molecular Biology, University Hospital Eppendorf, D-20246 Hamburg, Germany. heeren@uke.uni-hamburg.de
Grewal
T
T
Jäckle
S
S
Beisiegel
U
U
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000378:metabolism
D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011973:Receptors, LDL; D008071:Lipoprotein Lipase