title: ABCA1, ABCG1, and ABCG4 are distributed to distinct membrane meso-domains and disturb detergent-resistant domains on the plasma membrane.
abstract: ATP-binding cassette A1 (ABCA1), ABCG1, and ABCG4 are lipid transporters that mediate the efflux of cholesterol from cells. To analyze the characteristics of these lipid transporters, we examined and compared their distributions and lipid efflux activity on the plasma membrane. The efflux of cholesterol mediated by ABCA1 and ABCG1, but not ABCG4, was affected by a reduction of cellular sphingomyelin levels. Detergent solubility and gradient density ultracentrifugation assays indicated that ABCA1, ABCG1, and ABCG4 were distributed to domains that were solubilized by Triton X-100 and Brij 96, resistant to Triton X-100 and Brij 96, and solubilized by Triton X-100 but resistant to Brij 96, respectively. Furthermore, ABCG1, but not ABCG4, was colocalized with flotillin-1 on the plasma membrane. The amounts of cholesterol extracted by methyl-β-cyclodextrin were increased by ABCA1, ABCG1, or ABCG4, suggesting that cholesterol in non-raft domains was increased. Furthermore, ABCG1 and ABCG4 disturbed the localization of caveolin-1 to the detergent-resistant domains and the binding of cholera toxin subunit B to the plasma membrane. These results suggest that ABCA1, ABCG1, and ABCG4 are localized to distinct membrane meso-domains and disturb the meso-domain structures by reorganizing lipids on the plasma membrane; collectively, these observations may explain the different substrate profiles and lipid efflux roles of these transporters.
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Sano
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Ito
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kato
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kioka
authors.affiliation: Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hanada
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto, Japan; Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto, Japan; Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women's University, Kyoto, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Matsuo
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D000070996:ATP Binding Cassette Transporter, Subfamily G; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D017830:Octoxynol / Q000494:pharmacology; D009928:Organ Specificity
chemical_list: C419353:ABCG1 protein, human; C439766:ABCG4 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070996:ATP Binding Cassette Transporter, Subfamily G; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D003902:Detergents; D008563:Membrane Lipids; D008565:Membrane Proteins; C106354:flotillins; D017830:Octoxynol; D002784:Cholesterol