Stabilization of Caveolin-1 by Cellular Cholesterol and Scavenger Receptor Class B Type I

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• 作者：Philippe G. Frank ; Yves L. Marcel ; Margery A. Connelly ; Douglas M. Lublin ; Vivian Franklin ; David L. Williams ; and Michael P. Lisanti
• 刊名：Biochemistry
• 出版年：2002
• 出版时间：October 1, 2002
• 年：2002
• 卷：41
• 期：39
• 页码：11931 - 11940
• 全文大小：401K
• 年卷期：v.41,no.39(October 1, 2002)
• ISSN：1520-4995

文摘

Caveolae are 50-100 nm plasma membrane invaginations, which function in cell signaling,in transcytosis, and in regulating cellular cholesterol homeostasis. These subcompartments of the plasmamembrane are characterized by the presence of caveolin proteins. Recent studies have indicated that caveolaemay be involved in the regulation of cellular cholesterol efflux to high-density lipoproteins (HDL), aswell as selective cholesteryl ester uptake mediated by scavenger receptor class B type I (SR-BI). In thepresent studies, we show that caveolin-1 expression in HEK-293T cells has no effect on SR-BI-mediatedcellular cholesterol efflux to reconstituted HDL. However, SR-BI-mediated selective cholesteryl esteruptake is significantly inhibited by caveolin-1. Interestingly, we also found that SR-BI, but not CD36,can induce the dramatic stabilization of the caveolin-1 protein, independently of its transcriptional control.On the other hand, caveolin-1 has little effect on SR-BI stability, but clearly increases CD36 stability.Since SR-BI expression has been shown to increase cellular cholesterol levels, we next examined theeffect of cholesterol itself on caveolin-1 stabilization and localization. When cells were loaded withcholesterol, we observed the dramatic stabilization of caveolin-1 with significant clustering of caveolin-1at the cell surface. In addition, a palmitoylation-deficient caveolin-1 mutant was still responsive tocholesterol-induced stabilization, indicating that palmitoylation of caveolin-1 is not required for thecholesterol-induced stabilization of caveolin-1. These results suggest an important role for cholesteroland SR-BI in the regulation of caveolin functioning, especially in cell types such as endothelial cells andmacrophages, which can be dramatically affected by changes in their cholesterol content during thedevelopment of atherosclerosis.