Truncated apo B-70.5-containing lipoproteins bind to megalin but not the LDL receptor.
Apo B-100 of LDL can bind to both the LDL receptor and megalin, but the molecular interactions of apo B-100 with these 2 receptors are not completely understood. Naturally occurring mutant forms of apo B may be a source of valuable information on these interactions. Apo B-70.5 is uniquely useful because it contains the NH2-terminal portion of apo B-100, that includes only one of the two putative LDL receptor-binding sites (site A). The lipoprotein containing apo B-70. 5 (Lp B-70.5) was purified from apo B-100/apo B-70.5 heterozygotes by sequential ultracentrifugation combined with immunoaffinity chromatography. Cell culture experiments, ligand blot analysis, and in vivo studies all consistently showed that Lp B-70.5 is not recognized by the LDL receptor. The kidney was identified as a major organ in catabolism of Lp B-70.5 in New Zealand white rabbits. Autoradiographic analysis revealed that renal proximal tubular cells selectively removed Lp B-70.5. On ligand blotting of renal cortical membranes, Lp B-70.5 bound only to megalin. The ability of megalin to mediate cellular endocytosis of Lp B-70.5 was confirmed using retinoic acid/dibutyryl cAMP-treated F9 cells. This study suggests that the putative LDL receptor-binding site A on apo B-100 might not by itself be a functional binding domain and that the apo B-binding sites recognized by the LDL receptor and by megalin may be different. Moreover, megalin may play an important role in renal catabolism of apo B truncations, including apo B-70.5.
D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001345:Autoradiography; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D002460:Cell Line; D026541:Heymann Nephritis Antigenic Complex; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D014162:Transfection