The apoE isoform binding properties of the VLDL receptor reveal marked differences from LRP and the LDL receptor.
Apolipoprotein E (apoE) associates with lipoproteins and mediates their interaction with members of the LDL receptor family. ApoE exists as three common isoforms that have important distinct functional and biological properties. Two apoE isoforms, apoE3 and apoE4, are recognized by the LDL receptor, whereas apoE2 binds poorly to this receptor and is associated with type III hyperlipidemia. In addition, the apoE4 isoform is associated with the common late-onset familial and sporadic forms of Alzheimer's disease. Although the interaction of apoE with the LDL receptor is well characterized, the specificity of other members of this receptor family for apoE is poorly understood. In the current investigation, we have characterized the binding of apoE to the VLDL receptor and the LDL receptor-related protein (LRP). Our results indicate that like the LDL receptor, LRP prefers lipid-bound forms of apoE, but in contrast to the LDL receptor, both LRP and the VLDL receptor recognize all apoE isoforms. Interestingly, the VLDL receptor does not require the association of apoE with lipid for optimal recognition and avidly binds lipid-free apoE. It is likely that this receptor-dependent specificity for various apoE isoforms and for lipid-free versus lipid-bound forms of apoE is physiologically significant and is connected to distinct functions for these receptors.
Ruiz
Jose
J
Department of Surgery, University of Maryland School of Medicine, Rockville, MD 21201, USA.
Kouiavskaia
Diana
D
Migliorini
Molly
M
Robinson
Susan
S
Saenko
Evgueni L
EL
Gorlatova
Natalia
N
Li
Donghua
D
Lawrence
Daniel
D
Hyman
Bradley T
BT
Weisgraber
Karl H
KH
Strickland
Dudley K
DK
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D050356:Lipid Metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D025941:Protein Interaction Mapping; D011973:Receptors, LDL / Q000378:metabolism*; D020349:Surface Plasmon Resonance
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010446:Peptide Fragments; D011973:Receptors, LDL; C036053:VLDL receptor