title: Spontaneous reconstitution of discoidal HDL from sphingomyelin-containing model membranes by apolipoprotein A-I.
abstract: Nascent HDL is known to be formed by the interaction of apolipoprotein A-I (apoA-I) with transmembrane ABCA1, but the molecular mechanism by which nascent HDL forms is less well understood. Here, we studied how reconstituted high density lipoprotein (rHDL) forms spontaneously on the interaction of apoA-I with model membranes. The formation of rHDL from pure phosphatidylcholine (PC) large unilamellar vesicles (LUVs) proceeded very slowly at 37.0 degrees C, but sphingomyelin (SM) -rich PC/SM LUVs, which are in a gel/liquid-disordered phase (L(d) phase) at this temperature, were rapidly microsolubilized to form rHDL by apoA-I. The addition of cholesterol decreased the rate at which rHDL formed and induced the selective extraction of lipids by apoA-I, which preferably extracted lipids of L(d) phase rather than lipids of liquid-ordered phase. In addition, apoA-I extracted lipids from the outer and inner leaflets of LUVs simultaneously. These results suggest that the heterogeneous interface of the mixed membranes facilitates the insertion of apoA-I and induces L(d) phase-selective but leaflet-nonselective lipid extraction to form rHDL; they are compatible with recent cell works on apoA-I-dependent HDL generation.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fukuda
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakano
authors.forename: Supaporn
authors.initials: S
authors.lastname: Sriwongsitanont
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ueno
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Handa
mesh_terms: D016632:Apolipoprotein A-I / Q000378:metabolism*; D002784:Cholesterol / Q000494:pharmacology; D053442:High-Density Lipoproteins, Pre-beta / Q000096:biosynthesis*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008954:Models, Biological; D044367:Phase Transition; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D053835:Unilamellar Liposomes; D002784:Cholesterol