Low density lipoprotein receptors bind and mediate cellular catabolism of normal very low density lipoproteins in vitro.

摘要: Abstract Very low density lipoproteins (VLDL) are heterogeneous, triglyceride-rich particles that precursors of (LDL). Before conversion to LDL, the majority VLDL irreversibly cleared from plasma by uncertain mechanisms. To investigate one potential mechanism for clearance, we studied ability LDL receptors mediate uptake in vitro. Small, intermediate, and large normolipidemic humans were found bind undergo catabolism via on normal human fibroblasts. Binding cell surfaces was up-regulated lovastatin, an inducer receptors. Both a monoclonal antibody against receptor (IgG-C7) prevented binding 125I-VLDL. Also, mutant fibroblasts lacking low. Thus, mediated interactions with cells. affinity decreased near saturation, apparent number high sites increasing particle size. Because small (M(r) 115,000) relative 9-24 x 10(6)) clustered clathrin-coated pits, these findings suggest steric hindrance becomes important determinant saturation consistent lattice model receptor-ligand interactions. The capacity cellular size, model. also supported differences between 125I-VLDL partially purified solid-phase assays which constraints resulting clustering pits not present. In both cell-surface assays, bound apoE, apoB-100. Our studies establish interact due crowding is their catabolism. These may participate clearance vivo.