title: Functional implications of the influence of ABCA1 on lipid microenvironment at the plasma membrane: a biophysical study.
abstract: The ABCA1 transporter orchestrates cellular lipid homeostasis by promoting the release of cholesterol to plasmatic acceptors. The molecular mechanism is, however, unknown. We report here on the biophysical analysis in living HeLa cells of the ABCA1 lipid microenvironment at the plasma membrane. The modifications of membrane attributes induced by ABCA1 were assessed at both the outer and inner leaflet by monitoring either the lifetime of membrane inserted fluorescent lipid analogues by fluorescence lifetime imaging microscopy (FLIM) or, respectively, the membrane translocation of cationic sensors. Analysis of the partitioning of dedicated probes in plasma membrane blebs vesiculated from these cells allowed visualization of ABCA1 partitioning into the liquid disordered-like phase and corroborated the idea that ABCA1 destabilizes the lipid arrangement at the membrane. Specificity was demonstrated by comparison with cells expressing an inactive transporter. The physiological relevance of these modifications was finally demonstrated by the reduced membrane mobility and function of transferrin receptors under the influence of an active ABCA1. Collectively, these data assess that the control of both transversal and lateral lipid distribution at the membrane is the primary function of ABCA1 and positions the effluxes of cholesterol from cell membranes downstream to the redistribution of the sterol into readily extractable membrane pools.
authors.affiliation: Centre d'Immunologie de Marseille Luminy, Institut National de la Santè et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de la Méditerranée, Parc Scientifique de Luminy case 906, 13288 Marseille, Cedex 09 France.
authors.forename: Ana
authors.initials: A
authors.lastname: Zarubica
authors.forename: Anna Pia
authors.initials: AP
authors.lastname: Plazzo
authors.forename: Martin
authors.initials: M
authors.lastname: Stöckl
authors.forename: Tomasz
authors.initials: T
authors.lastname: Trombik
authors.forename: Yannick
authors.initials: Y
authors.lastname: Hamon
authors.forename: Peter
authors.initials: P
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Pomorski
authors.forename: Andreas
authors.initials: A
authors.lastname: Herrmann
authors.forename: Giovanna
authors.initials: G
authors.lastname: Chimini
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D006367:HeLa Cells; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008856:Microscopy, Fluorescence / Q000379:methods; D008969:Molecular Sequence Data; D011990:Receptors, Transferrin / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008055:Lipids; D011990:Receptors, Transferrin