Sphingomyelin-dependence of cholesterol efflux mediated by ABCG1

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

Division of Applied Life Sciences, Kyoto University, Kyoto 606-8502

Corresponding Author: 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 sphingomyelin level is reduced because of a mutation of 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- $beta$ -cyclodextrin suggested that cholesterol in non-raft 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.

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