ATP-binding cassette transporters are enriched in non-caveolar detergent-insoluble glycosphingolipid-enriched membrane domains (DIGs) in human multidrug-resistant cancer cells.
In this study we show that P-glycoprotein in multidrug-resistant 2780AD human ovarian carcinoma cells and multidrug resistance-associated protein 1 in multidrug-resistant HT29col human colon carcinoma cells are predominantly located in Lubrol-based detergent-insoluble glycosphingolipid-enriched membrane domains. This localization is independent of caveolae, since 2780AD cells do not express caveolin-1. Although HT29col cells do express caveolin-1, the ATP-binding cassette transporter and caveolin-1 were dissociated on the basis of differential solubility in Triton X-100 and absence of microscopical colocalization. While both the multidrug resistance-associated protein 1 and caveolin-1 are located in Lubrol-based membrane domains, they occupy different regions of these domains.
Hinrichs
John W J
JW
Department of Membrane Cell Biology, Groningen University Institute for Drug Exploration, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Klappe
Karin
K
Hummel
Ina
I
Kok
Jan W
JW
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000737:chemistry*; D021941:Caveolae / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D019742:Chemokines, CC / Q000096:biosynthesis*; D003902:Detergents / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D006028:Glycosphingolipids / Q000737:chemistry; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017830:Octoxynol / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D019742:Chemokines, CC; D003902:Detergents; D006028:Glycosphingolipids; C070959:Ccl6 protein, mouse; D011092:Polyethylene Glycols; C005092:lubrol; D000255:Adenosine Triphosphate; D017830:Octoxynol