title: ATP-binding cassette transporter A1 expression disrupts raft membrane microdomains through its ATPase-related functions.
abstract: ATP-binding cassette transporter A1 (ABCA1) is known to mediate cholesterol efflux to lipid-poor apolipoprotein A-I. In addition, ABCA1 has been shown to influence functions of the plasma membrane, such as endocytosis and phagocytosis. Here, we report that ABCA1 expression results in a significant redistribution of cholesterol and sphingomyelin from rafts to non-rafts. Caveolin, a raft/caveolae marker also redistributes from punctate caveolae-like structures to the general area of the plasma membrane upon ABCA1 expression. Furthermore, we observed significant reduction of Akt activation in ABCA1-expressing cells, consistent with raft disruption. Cholesterol content in the plasma membrane is, however, not altered. Moreover, we provide evidence that a non-functional ABCA1 with mutation in an ATP-binding domain, A937V, fails to redistribute cholesterol, sphingomyelin, or caveolin. A937V also fails to influence Akt activation. Finally, we show that apolipoprotein A-I preferentially associates with non-raft membranes in ABCA1-expressing cells. Our results thus demonstrate that ABCA1 causes a change in overall lipid packing of the plasma membrane, likely through its ATPase-related functions. Such reorganization by ABCA1 effectively expands the non-raft membrane fractions and, consequentially, pre-conditions cells for cholesterol efflux.
authors.affiliation: Ottawa Health Research Institute and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1Y 4E9, Canada.
authors.forename: Yves D
authors.initials: YD
authors.lastname: Landry
authors.forename: Maxime
authors.initials: M
authors.lastname: Denis
authors.forename: Shilpi
authors.initials: S
authors.lastname: Nandi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bell
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Vaughan
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zha
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D051242:Caveolin 1 / Q000096:biosynthesis; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D004705:Endocytosis; D021962:Membrane Microdomains / Q000737:chemistry*; D026901:Membrane Transport Proteins / Q000737:chemistry; D008856:Microscopy, Fluorescence; D010743:Phospholipids / Q000737:chemistry; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D051242:Caveolin 1; D026901:Membrane Transport Proteins; D010743:Phospholipids; D014168:Transferrin; D002784:Cholesterol; D051057:Proto-Oncogene Proteins c-akt