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Papers In Press, published online ahead of print November 1, 2007
J. Lipid Res., doi:10.1194/jlr.M700139-JLR200

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Journal of Lipid Research, Vol. 48, 2377-2384, November 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Sphingomyelin-dependence of cholesterol efflux mediated by ABCG1

Osamu Sano^*, Aya Kobayashi^*, Kohjiro Nagao^*, Keigo Kumagai, Noriyuki Kioka^*, Kentaro Hanada, Kazumitsu Ueda^1,* and Michinori Matsuo^*

^* Laboratory of Cellular Biochemistry, Division of Applied Life Sciences, Kyoto University Graduate School of Agriculture, Kyoto 606-8502, Japan
Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of four figures.

Published, JLR Papers in Press, August 29, 2007.

¹ To whom correspondence should be addressed. e-mail: uedak{at}kais.kyoto-u.ac.jp

ABCG1, one of the half-type ATP binding cassette (ABC) proteins, mediates the efflux of cholesterol to HDL and functions in the reverse cholesterol transport from peripheral cells to the liver. We have shown that ABCG1 mediates the efflux of not only cholesterol but also sphingomyelin (SM) and phosphatidylcholine. Because SM preferentially associates with cholesterol, we examined whether it plays an important role in the ABCG1-mediated efflux of cholesterol. The efflux of cholesterol and SM mediated by ABCG1 was reduced in a mutant CHO-K1 cell line, LY-A, in which the cellular SM level is reduced because of a mutation of the ceramide transfer protein CERT. In contrast, CHO-K1 cells overexpressing CERT showed an increased efflux of cholesterol and SM mediated by ABCG1. The sensitivity of cells to methyl-ß-cyclodextrin suggested that cholesterol in nonraft domains was increased due to the disruption of raft domains in LY-A cells. These results suggest that the ABCG1-mediated efflux of cholesterol and SM is dependent on the cellular SM level and distribution of cholesterol in the plasma membrane.

Supplementary key words ATP binding cassette A1 • ceramide transfer protein • detergent-resistant membrane • raft

Abbreviations: ABC, ATP binding cassette; apoA-I, apolipoprotein A-I; CHO, Chinese hamster ovary; LXR, liver X receptor; MßCD, methyl-ß-cyclodextrin; PC, phosphatidylcholine; SM, sphingomyelin; SR-BI, scavenger receptor class B type I

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