Spontaneous reconstitution of discoidal HDL from sphingomyelin-containing model membranes by apolipoprotein A-I
Spontaneous reconstitution of discoidal HDL from sphingomyelin-containing model membranes by apolipoprotein A-I
复制标题
DOI：
10.1194/jlr.m600495-jlr200
复制
发表时间：
2007-04-01
影响因子：
6.5
通讯作者：
Handa, Tetsurou
中科院分区：
文献类型：
--
作者：
Fukuda, Masakazu;Nakano, Minoru;Handa, Tetsurou
已知新生高密度脂蛋白是由载脂蛋白A-I(apoA-I)与跨膜ABCA1相互作用形成的，但新生高密度脂蛋白形成的分子机制尚不清楚。在这里，我们研究了重组高密度脂蛋白(RHDL)是如何在载脂蛋白A-I与模型膜相互作用时自发形成的。纯磷脂酰胆碱(PC)大单层囊泡(LUV)在37.0℃时形成rHDL的过程非常缓慢，但在此温度下处于凝胶/液体无序相(L-d相)的富含鞘磷脂(SM)的PC/SM LUV迅速被apoA-I微溶形成rHDL.胆固醇的加入降低了重组人高密度脂蛋白的形成速度，并诱导apoA-I选择性地提取脂类，apoA-I优先提取L-d相脂类，而不是液体有序相脂类。此外，apoA-I同时从狼疮外叶和内叶中提取脂类。这些结果表明，混合膜的异质界面促进了载脂蛋白A-I的插入，并诱导L-d相选择性而非叶选择性的脂类提取物形成重组高密度脂蛋白，这与细胞最近关于载脂蛋白A-I依赖的高密度脂蛋白生成的工作是一致的。
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.