This Article Full Text Full Text (PDF) All Versions of this Article: 26/3/442    most recent 01.ATV.0000201282.64751.47v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Heeren, J. Articles by Grewal, T. Search for Related Content PubMed PubMed Citation Articles by Heeren, J. Articles by Grewal, T. Pubmed/NCBI databases Genetics Home Reference Related Collections Pathophysiology Cell biology/structural biology Lipid and lipoprotein metabolism

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:442.)
© 2006 American Heart Association, Inc.

Brief Reviews

Apolipoprotein E Recycling

Implications for Dyslipidemia and Atherosclerosis

Joerg Heeren; Ulrike Beisiegel; Thomas Grewal

From the Institute for Biochemistry and Molecular Biology II (J.H., U.B.), Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; and Centre for Immunology (T.G.), St. Vincent’s Hospital, University of New South Wales, Darlinghurst, Sydney, Australia.

Correspondence to Dr Joerg Heeren, IBM II, Molecular Cell Biology, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. E-mail heeren{at}uke.uni-hamburg.de

After receptor-mediated endocytosis, the intracellular fate of triglyceride-rich lipoproteins (TRLs) is far more complex than the classical degradation pathway of low-density lipoproteins. Once internalized, TRLs disintegrate in peripheral endosomes, followed by a differential sorting of TRL components. Although core lipids and apolipoprotein B are targeted to lysosomes, the majority of TRL-derived apolipoprotein E (apoE) remains in peripheral recycling endosomes. This pool of TRL-derived apoE is then mobilized by high-density lipoproteins (HDLs) or HDL-derived apoA-I to be recycled back to the plasma membrane, followed by apoE resecretion and the subsequent formation of apoE-containing HDL. The HDL-induced recycling of apoE is accompanied by cholesterol efflux and involves the internalization and targeting of HDL-derived apoA-I to endosomes containing both apoE and cholesterol. These findings point to a yet unknown intracellular link between TRL-derived apoE, cellular cholesterol transport, and HDL metabolism. Recent studies provide first evidence that impaired recycling of TRL-derived apoE4, but not apoE3, is associated with intracellular cholesterol accumulation, which might explain some well-documented effects of apoE4 on HDL metabolism. This review summarizes the current understanding of apoE recycling and its potential role in the regulation of plasma apoE levels in the postprandial state.

Key Words: apolipoprotein E • HDL • endocytosis • cholesterol efflux • triglyceride-rich lipoproteins

This article has been cited by other articles:

				B. W. Parks, R. Srivastava, S. Yu, and J. H.S. Kabarowski ApoE-Dependent Modulation of HDL and Atherosclerosis by G2A in LDL Receptor-Deficient Mice Independent of Bone Marrow-Derived Cells Arterioscler Thromb Vasc Biol, April 1, 2009; 29(4): 539 - 547. [Abstract] [Full Text] [PDF]

				G. S. Getz and C. A. Reardon Apoprotein E as a lipid transport and signaling protein in the blood, liver, and artery wall J. Lipid Res., April 1, 2009; 50(Supplement): S156 - S161. [Abstract] [Full Text] [PDF]

				M. A. Ruby, D. K. Nomura, C. S. S. Hudak, L. M. Mangravite, S. Chiu, J. E. Casida, and R. M. Krauss Overactive endocannabinoid signaling impairs apolipoprotein E-mediated clearance of triglyceride-rich lipoproteins PNAS, September 23, 2008; 105(38): 14561 - 14566. [Abstract] [Full Text] [PDF]

				S. K. Nilsson, S. Christensen, M. K. Raarup, R. O. Ryan, M. S. Nielsen, and G. Olivecrona Endocytosis of Apolipoprotein A-V by Members of the Low Density Lipoprotein Receptor and the Vps10p Domain Receptor Families J. Biol. Chem., September 19, 2008; 283(38): 25920 - 25927. [Abstract] [Full Text] [PDF]

				N. Tiffin, I. Okpechi, C. Perez-Iratxeta, M. A. Andrade-Navarro, and R. Ramesar Prioritization of candidate disease genes for metabolic syndrome by computational analysis of its defining phenotypes Physiol Genomics, September 17, 2008; 35(1): 55 - 64. [Abstract] [Full Text] [PDF]

				M. Kockx, W. Jessup, and L. Kritharides Regulation of Endogenous Apolipoprotein E Secretion by Macrophages Arterioscler Thromb Vasc Biol, June 1, 2008; 28(6): 1060 - 1067. [Abstract] [Full Text] [PDF]

				M. Heller, E. Schlappritzi, D. Stalder, J.-M. Nuoffer, and A. Haeberli Compositional Protein Analysis of High Density Lipoproteins in Hypercholesterolemia by Shotgun LC-MS/MS and Probabilistic Peptide Scoring Mol. Cell. Proteomics, June 1, 2007; 6(6): 1059 - 1072. [Abstract] [Full Text] [PDF]