The apoE isoform binding properties of the VLDL receptor reveal marked differences from LRP and the LDL receptor

Journal of Lipid Research

Bradley T. Hyman¹  Diana Kouiavskaia²  Evgueni L. Saenko²  Daniel Lawrence³  Jose Ruiz³  Molly Migliorini³  Natalia Gorlatova³  Donghua Li³  Susan Robinson³  Karl H. Weisgraber⁴  Dudley K. Strickland⁵ 

[1] Alzheimer Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129;Department of Biochemistry, University of Maryland School of Medicine, Rockville, MD 21201;Department of Surgery, University of Maryland School of Medicine, Rockville, MD 21201;Gladstone Institutes of Cardiovascular Disease and Neurological Disease, Cardiovascular Research Institute, and Department of Pathology, University of California, San Francisco, CA 94141;To whom correspondence should be addressed.;

关键词: apolipoprotein E;    low density lipoprotein;    very low density lipoprotein;    low density lipoprotein receptor-related protein;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown