Characterization of chylomicron remnant binding to rat liver membranes.

The binding of chylomicron remnants to rat liver membranes was investigated using radioiodinated lipoproteins. The specific activity of binding increased in parallel with increased enrichment in plasma membrane markers. The yield of receptor activity, however, decreased with enrichment. Accordingly, a partially purified plasma membrane preparation was used for routine studies. Binding was saturable, with half maximal binding achieved at 4.6 micro g tetramethylurea-precipitable protein per ml. The rate of binding was time- and temperature-dependent. It could be inhibited only moderately by 10 mM EDTA. Chylomicron remnants appeared to bind to the membrane as a unit. The bound particle was richer in apoproteins of 20,000-50,000 molecular weight relative to low molecular weight apoproteins than the particles that were not bound. Lipoprotein particles containing only human apoB did not bind to liver membranes nor did they compete for the remnant binding site. Rat lipoproteins of d 1.019-1.063 g/ml did compete for remnant binding. When they were separated into apoB-rich (LDL) or apoE-rich (HDL(c)) fractions by block electrophoresis, the apoE-rich fraction was a more potent competitor. ApoE purified and reconstituted into dimyristoyl phosphatidylcholine vesicles was a potent competitor for the remnant binding site. Vesicles containing (125)I-labeled apoE bound to the membranes, and they could be displaced by unlabeled remnants. Dimyristoyl phosphatidylcholine vesicles themselves did not compete with either remnants or apoE-phospholipid vesicles. These results offer strong support for the hypothesis that the liver membrane chylomicron remnant receptor recognizes apoE with a high affinity, and this initiates the rapid removal of lipoproteins that contain this apoprotein.-Cooper, A. D., S. K. Erickson, R. Nutik, and M. A. Shrewsbury. Characterization of chylomicron remnant binding to rat liver membranes.