Very-low-density lipoprotein binding to the apolipoprotein E receptor 2 isenhanced by lipoprotein lipase, and does not require apolipoprotein E

The apolipoprotein (apo)E receptor 2 (apoER2) is a recently cloned member o f the low-density lipoprotein (LDL) receptor (LDLR) family, showing a high homology with both the LDLR and the very-low-density lipoprotein (VLDL) rec eptor (VLDLR), In the present study, the binding characteristics of the apo ER2 with respect to apoE and lipoprotein lipase (LPL) were investigated. VL DL was isolated from both apoE-deficient mice and mice expressing the human APOE2 (Arg(158)-->Cys) and APOE3-Leiden isoforms on an Apoe(-/-),Ldlr(-/-) double knock-out background, apoE-rich rabbit beta-VLDL was used as a posi tive control for binding. Binding experiments performed with Chinese hamste r ovary cells expressing the human apoER2 showed that the receptor was able to bind VLDL containing either of the apoE isoforms, as well as the apoE-d eficient VLDL. Hence, in contrast with the VLDLR, the apoER2 is not strictl y dependent on apoE for VLDL binding. Since LPL has been shown to enhance t he binding of lipoproteins to several members of the LDLR family, including the LDLR-related protein, VLDL receptor, gp330 and the LDLR itself, VLDL b inding experiments were performed in the presence of LPL, Addition of LPL r esulted in a significant increase in apoER2 binding for all VLDL fractions used in this study. In conclusion, lipoprotein binding of VLDL to the apoER 2 is enhanced in the presence of LPL, and is not restricted to apoE-contain ing lipoproteins.