Truncated apo B-70.5-containing lipoproteins bind to megalin but not the LDL receptor

被引:26
作者
Chen, ZJ
Saffitz, JE
Latour, MA
Schonfeld, G
机构
[1] Washington Univ, Sch Med, Dept Med, Div Atherosclerosis Lipid Res & Nutr, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA
关键词
D O I
10.1172/JCI4921
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 B100/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.
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页码:1419 / 1430
页数:12
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