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A more recent version of this article appeared on April 1, 2007

Papers In Press, published online ahead of print January 15, 2007
J. Lipid Res., doi:10.1194/jlr.M600495-JLR200
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Submitted on November 17, 2006
Revised on December 20, 2006
Accepted on January 14, 2007

Spontaneous reconstitution of discoidal HDL from sphingomyelin-containing model membranes by apolipoprotein A-I

Masakazu Fukuda, Minoru Nakano, Supaporn Sriwongsitanont, Masaharu Ueno, Yoshihiro Kuroda, and Tetsurou Handa

Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501

Corresponding Author: mnakano{at}pharm.kyoto-u.ac.jp

Nascent high-density lipoprotein (HDL) is known to be formed by the interaction of apolipoprotein A-I (apoA-I) with transmembrane ATP-binding cassette transporter A1, but the molecular mechanism by which nascent HDL forms is less well understood. Here, we studied how reconstituted HDL (rHDL) forms spontaneously on the interaction of apoA-I with model membranes. The formation of rHDL from pure phosphatidylcholine (PC) LUV proceeded very slowly at 37.0ºC, but sphingomyelin (SM) -rich PC/SM LUVs, which are in a gel/liquid-disordered (Ld) 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 Ld phase rather than lipids of Lo phase. In addition, apoA-I extracted lipids from the outer and inner leaflets of LUVs simultaneously. These results suggest that heterogeneous interface of the mixed membranes facilitates the insertion of apoA-I and induces Ld phase-selective but leaflet-nonselective lipid extraction to form rHDL, and are compatible with recent cell works on the apoA-I-dependent HDL generation.


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C. Vedhachalam, P. T. Duong, M. Nickel, D. Nguyen, P. Dhanasekaran, H. Saito, G. H. Rothblat, S. Lund-Katz, and M. C. Phillips
Mechanism of ATP-binding Cassette Transporter A1-mediated Cellular Lipid Efflux to Apolipoprotein A-I and Formation of High Density Lipoprotein Particles
J. Biol. Chem., August 24, 2007; 282(34): 25123 - 25130.
[Abstract] [Full Text] [PDF]


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