SR-BI Mediates Cholesterol Efflux via Its Interactions with Lipid-Bound ApoE. Structural Mutations in SR-BI Diminish Cholesterol Efflux
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- 作者：Angeliki Chroni ; Thomas J. F. Nieland ; Kyriakos E. Kypreos ; Monty Krieger ; and Vassilis I. Zannis
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：October 4, 2005
- 年：2005
- 卷：44
- 期：39
- 页码：13132 - 13143
- 全文大小：211K
- 年卷期：v.44,no.39(October 4, 2005)
- ISSN：1520-4995
文摘
Apolipoprotein E (apoE) and the lipoprotein receptor SR-BI play critical roles in lipid andlipoprotein metabolism. We have examined the cholesterol efflux from wild-type (WT) and mutant formsof SR-BI expressed in ldlA-7 cells using reconstituted discoidal particles consisting of apoE, 1-palmitoyl-2-oleoyl-L-phospatidylcholine (POPC), and cholesterol (C) as acceptors. POPC/C-apoE particles generatedusing apoE2, apoE3, apoE4, or carboxy-terminally truncated forms apoE4-165, apoE4-202, apoE4-229,and apoE4-259 caused similar (20-25%) cholesterol efflux from WT SR-BI. Cholesterol efflux mediatedby POPC/C-apoE was not enhanced in the presence of lipid-free apoE. The rate of cholesterol effluxmediated by particles containing the WT or carboxy-terminally truncated forms of apoE was decreasedto approximately 30% of the WT control with the Q402R/Q418R mutant SR-BI form that is unable tobind native HDL normally but binds LDL. The rate of cholesterol efflux was further decreased toapproximately 7% of the WT control with another SR-BI mutant (M158R) that binds neither HDL norLDL. The level of binding of POPC/C-apoE particles (150 
f">g/mL) to SR-BI mutant forms Q402R/Q418R and M158R was 70 and 8% of the WT control, respectively. SR-BI-dependent binding of lipid-free apoE to cells was undetectable, and cholesterol efflux was less than 0.5%. The findings establish thatonly lipid-bound apoE promotes SR-BI-mediated cholesterol efflux and that the amino-terminal region ofresidues 1-165 of apoE is sufficient for both receptor binding and cholesterol efflux. The SR-BI-apoEinteractions may contribute to overall cholesterol homeostasis in cells and tissues that express SR-BI andapoE.
f">g/mL) to SR-BI mutant forms Q402R/Q418R and M158R was 70 and 8% of the WT control, respectively. SR-BI-dependent binding of lipid-free apoE to cells was undetectable, and cholesterol efflux was less than 0.5%. The findings establish thatonly lipid-bound apoE promotes SR-BI-mediated cholesterol efflux and that the amino-terminal region ofresidues 1-165 of apoE is sufficient for both receptor binding and cholesterol efflux. The SR-BI-apoEinteractions may contribute to overall cholesterol homeostasis in cells and tissues that express SR-BI andapoE.