Sphingomyelin-dependence of cholesterol efflux mediated by ABCG1.
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-beta-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.
Sano
Osamu
O
Laboratory of Cellular Biochemistry, Division of Applied Life Sciences, Kyoto University Graduate School of Agriculture, Kyoto, Japan.
Kobayashi
Aya
A
Nagao
Kohjiro
K
Kumagai
Keigo
K
Kioka
Noriyuki
N
Hanada
Kentaro
K
Ueda
Kazumitsu
K
Matsuo
Michinori
M
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D016466:CHO Cells; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D006367:HeLa Cells; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D013109:Sphingomyelins / Q000502:physiology*; D047392:beta-Cyclodextrins / Q000494:pharmacology
C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D013109:Sphingomyelins; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol; C119090:CERT1 protein, human; D017346:Protein Serine-Threonine Kinases