| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Departments of Surgery, University of Maryland School of Medicine, Rockville, MD 21201
Biochemistry, University of Maryland School of Medicine, Rockville, MD 21201
Alzheimer Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129
** Gladstone Institutes of Cardiovascular Disease and Neurological Disease, Cardiovascular Research Institute, and Department of Pathology, University of California, San Francisco, CA 94141
Published, JLR Papers in Press, May 1, 2005. DOI 10.1194/jlr.M500114-JLR200
1 To whom correspondence should be addressed. e-mail: dstrickland{at}som.umaryland.edu
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.
Abbreviations: AD, Alzheimer's disease; apoE, apolipoprotein E; LRP, low density lipoprotein receptor-related protein; RAP, receptor-associated protein; Rmax, maximal change in response units; RU, resonance units; SPR, surface plasmon resonance; sVLDLr1–8, soluble very low density lipoprotein receptor fragment containing ligand binding repeats 1–8
Supplementary key words apolipoprotein E • low density lipoprotein • very low density lipoprotein • low density lipoprotein receptor-related protein
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Oganesian, L. C. Armstrong, M. M. Migliorini, D. K. Strickland, and P. Bornstein Thrombospondins Use the VLDL Receptor and a Nonapoptotic Pathway to Inhibit Cell Division in Microvascular Endothelial Cells Mol. Biol. Cell, February 1, 2008; 19(2): 563 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Zemskov, I. Mikhailenko, D. K. Strickland, and A. M. Belkin Cell-surface transglutaminase undergoes internalization and lysosomal degradation: an essential role for LRP1 J. Cell Sci., September 15, 2007; 120(18): 3188 - 3199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fan, S. Qiu, C. D. Overton, P. G. Yancey, L. L. Swift, W. G. Jerome, M. F. Linton, and S. Fazio Impaired Secretion of Apolipoprotein E2 from Macrophages J. Biol. Chem., May 4, 2007; 282(18): 13746 - 13753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hayashi, R. B. Campenot, D. E. Vance, and J. E. Vance Apolipoprotein E-Containing Lipoproteins Protect Neurons from Apoptosis via a Signaling Pathway Involving Low-Density Lipoprotein Receptor-Related Protein-1 J. Neurosci., February 21, 2007; 27(8): 1933 - 1941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Zerbinatti, S. E. Wahrle, H. Kim, J. A. Cam, K. Bales, S. M. Paul, D. M. Holtzman, and G. Bu Apolipoprotein E and Low Density Lipoprotein Receptor-related Protein Facilitate Intraneuronal Abeta42 Accumulation in Amyloid Model Mice J. Biol. Chem., November 24, 2006; 281(47): 36180 - 36186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Koldamova, M. Staufenbiel, and I. Lefterov Lack of ABCA1 Considerably Decreases Brain ApoE Level and Increases Amyloid Deposition in APP23 Mice J. Biol. Chem., December 30, 2005; 280(52): 43224 - 43235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Wahrle, H. Jiang, M. Parsadanian, R. E. Hartman, K. R. Bales, S. M. Paul, and D. M. Holtzman Deletion of Abca1 Increases Abeta Deposition in the PDAPP Transgenic Mouse Model of Alzheimer Disease J. Biol. Chem., December 30, 2005; 280(52): 43236 - 43242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Hirsch-Reinshagen, L. F. Maia, B. L. Burgess, J.-F. Blain, K. E. Naus, S. A. McIsaac, P. F. Parkinson, J. Y. Chan, G. H. Tansley, M. R. Hayden, et al. The Absence of ABCA1 Decreases Soluble ApoE Levels but Does Not Diminish Amyloid Deposition in Two Murine Models of Alzheimer Disease J. Biol. Chem., December 30, 2005; 280(52): 43243 - 43256. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
