Interaction of apo E-containing lipoproteins with the LDL receptor-related protein LRP.
The low-density lipoprotein (LDL) receptor-related protein (LRP) is a multifunctional cell surface receptor that interacts with apolipoprotein E (apo E)-rich lipoproteins, and alpha2-macroglobulin (alpha2-M) in the activated state (alpha2-M*). Whether LRP is a physiologically relevant lipoprotein receptor for naturally occurring apo E-rich lipoproteins, however, is still under discussion. To address this question, we isolated beta-migrating very low density lipoprotein (beta-VLDL) from rabbits by using gel filtration chromatography. Biochemical analysis of beta-VLDL subfractions demonstrated that we isolated apo E- and cholesterol-rich triglycerides with differences in composition and size. Binding and uptake characteristics of beta-VLDL subfractions and alpha2-M* on mouse peritoneal macrophages (MPM) and Hep G2 cells were examined by electron microscopy. One of the beta-VLDL subfractions, beta-VLDL(II), bound specifically to LRP on MPM and Hep G2. beta-VLDL(II) competed with the binding of alpha2-M* without addition of exogenous apo E. Furthermore, binding and uptake of beta-VLDL(II) and alpha2-M* were not affected by either lactoferrin or Ca2+-free medium. The results indicate that naturally occurring apo E-rich lipoproteins do exist and that they very likely interact with LRP via the same binding site as alpha2-M*.
Küchenhoff
A
A
Institute for Arteriosclerosis Research, University of Münster, Germany.
Harrach-Ruprecht
B
B
Robenek
H
H
D000818:Animals; D001057:Apolipoproteins E / Q000032:analysis / Q000378:metabolism*; D001667:Binding, Competitive; D002784:Cholesterol / Q000032:analysis; D003470:Culture Media; D006651:Histocytochemistry; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology; D008074:Lipoproteins / Q000302:isolation & purification / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000737:chemistry / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D011817:Rabbits; D011971:Receptors, Immunologic / Q000378:metabolism*; D014280:Triglycerides / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000648:ultrastructure
D001057:Apolipoproteins E; D003470:Culture Media; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D014280:Triglycerides; D002784:Cholesterol; D007781:Lactoferrin