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Journal of Lipid Research, Vol. 48, 2560-2570, December 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Distinct mechanisms for OxLDL uptake and cellular trafficking by class B scavenger receptors CD36 and SR-BI

Bing Sun^1,*, Boris B. Boyanovsky^1,, Margery A. Connelly, Preetha Shridas, Deneys R. van der Westhuyzen^*,,** and Nancy R. Webb^2,*,

^* Graduate Center for Nutritional Sciences, University of Kentucky Medical Center, Lexington, KY 40536
Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536
^** Department of Molecular and Cellular Biochemistry, University of Kentucky Medical Center, Lexington, KY 40536
Johnson & Johnson Pharmaceutical Research and Development, LLC, Spring House, PA 19477-0776

Published, JLR Papers in Press, September 19, 2007.

¹ B. Sun and B. B. Boyanovsky contributed equally to this work.

² To whom correspondence should be addressed. e-mail: nrwebb1{at}uky.edu

Modified forms of LDL, including oxidized low density lipoprotein (OxLDL), contribute to macrophage lipid accumulation in the vessel wall. Despite the pathophysiological importance of uptake pathways for OxLDL, the molecular details of OxLDL endocytosis by macrophages are not well understood. Studies in vitro demonstrate that the class B scavenger receptor CD36 mediates macrophage uptake and degradation of OxLDL. Although the closely related scavenger receptor class B type I (SR-BI) binds OxLDL with high affinity, evidence that SR-BI plays a role in OxLDL metabolism is lacking. In this study, we directly compared OxLDL uptake and degradation by CD36 and SR-BI. Our results indicate that although CD36 and SR-BI internalize OxLDL, SR-BI mediates significantly less OxLDL degradation. Endocytosis of OxLDL by both SR-BI and CD36 is independent of caveolae, microtubules, and actin cytoskeleton. However, OxLDL uptake by CD36, but not SR-BI, is dependent on dynamin. The analysis of chimeric SR-BI/CD36 receptors shows that the CD36 C-terminal cytoplasmic tail is necessary and sufficient for dynamin-dependent OxLDL internalization by class B scavenger receptors. These findings indicate that different mechanisms are involved in OxLDL uptake by SR-BI and CD36, which may segregate these two structurally homologous receptors at the cell surface, leading to differences in intracellular trafficking and degradation.

Supplementary key words atherosclerosis • endocytosis • dynamin • scavenger receptor class B type I • oxidized low density lipoprotein

Abbreviations: CHO, Chinese hamster ovary; MFI, mean fluorescence intensity; OxLDL, oxidized low density lipoprotein; SR-BI, scavenger receptor class B type I; VSMC, vascular smooth muscle cell

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