title: Membrane binding sites for plasma lipoproteins on endosomes from rat liver.
abstract: Highly purified endosomal membranes from rat liver, enriched in receptors for a number of macromolecules taken up into hepatocytes via the coated pit/endosome/lysosome pathway [including the receptor for low density lipoproteins (LDL)], were used to characterize binding sites for lipoproteins containing apolipoprotein E. In endosomal membranes from livers of estradiol-treated rats, in which LDL receptors are induced manyfold, two high-affinity binding sites were found for two apolipoprotein E-rich lipoproteins: very low density beta-lipoproteins (beta-VLDL) from cholesterol-fed rabbits and rat chylomicron remnants. One of these sites, binding to which is inhibited by 30 mM EDTA, appears identical to the LDL receptor by ligand and immunoblotting and other characteristics. The other site, highly resistant to EDTA, does not bind LDL. Binding to the EDTA-resistant site, however, is readily inhibited by heparin (as is the LDL receptor) and also by antisera prepared against rat or bovine LDL receptor. The distribution of the EDTA-resistant site among early endosomes, late endosomes, and endosome-derived receptor-recycling membranes is similar to that of the LDL receptor and other recycling receptors. The LDL receptor was present in endosomal membranes from livers of untreated rats at about 10% of the level found in membranes from estradiol-treated rats, but the EDTA-resistant site was barely detectable. No saturable binding of beta-VLDL that could not be inhibited by antisera to the LDL receptor could be detected in endosomal membranes from livers of either untreated or estradiol-treated rats. The EDTA-resistant site may be a modified form of the LDL receptor that recognizes apolipoprotein E but not the B apolipoprotein of LDL. Alternatively, it may be a distinct receptor sharing immunological determinants with the LDL receptor, specialized for the endocytosis of certain lipoproteins containing apolipoprotein E, including chylomicron remnants.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
authors.forename: S
authors.initials: S
authors.lastname: Jaeckle
authors.forename: S E
authors.initials: SE
authors.lastname: Brady
authors.forename: R J
authors.initials: RJ
authors.lastname: Havel
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D004705:Endocytosis; D004958:Estradiol / Q000494:pharmacology; D015151:Immunoblotting; D007425:Intracellular Membranes / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure*; D008297:Male; D015388:Organelles / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism; D018110:Receptors, Lipoprotein
chemical_list: D001057:Apolipoproteins E; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D004958:Estradiol; D004492:Edetic Acid