Very-low-density lipoprotein binding to the apolipoprotein E receptor 2 is enhanced by lipoprotein lipase, and does not require apolipoprotein E.
The apolipoprotein (apo)E receptor 2 (apoER2) is a recently cloned member of the low-density lipoprotein (LDL) receptor (LDLR) family, showing a high homology with both the LDLR and the very-low-density lipoprotein (VLDL) receptor (VLDLR). In the present study, the binding characteristics of the apoER2 with respect to apoE and lipoprotein lipase (LPL) were investigated. VLDL 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 positive control for binding. Binding experiments performed with Chinese hamster 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-deficient VLDL. Hence, in contrast with the VLDLR, the apoER2 is not strictly dependent on apoE for VLDL binding. Since LPL has been shown to enhance the binding of lipoproteins to several members of the LDLR family, including the LDLR-related protein, VLDL receptor, gp330 and the LDLR itself, VLDL binding experiments were performed in the presence of LPL. Addition of LPL resulted in a significant increase in apoER2 binding for all VLDL fractions used in this study. In conclusion, lipoprotein binding of VLDL to the apoER2 is enhanced in the presence of LPL, and is not restricted to apoE-containing lipoproteins.
Tacken
P J
PJ
Department of Human and Clinical Genetics, Leiden University Medical Center, P.O. Box 9503, 2300 RA, Leiden, The Netherlands.
Beer
F D
FD
Vark
L C
LC
Havekes
L M
LM
Hofker
M H
MH
Willems Van Dijk K
D000818:Animals; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D005508:Food Deprivation; D017353:Gene Deletion; D026502:LDL-Receptor Related Proteins; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism*
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D026502:LDL-Receptor Related Proteins; D008079:Lipoproteins, VLDL; D018110:Receptors, Lipoprotein; C052720:apolipoprotein E3 (Leidein); C098773:low density lipoprotein receptor-related protein 8; D008071:Lipoprotein Lipase