Specific docking of apolipoprotein A-I at the cell surface requires a functional ABCA1 transporter
Specific docking of apolipoprotein A-I at the cell surface requires a functional ABCA1 transporter
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DOI：
10.1074/jbc.m010265200
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发表时间：
2001-03-30
影响因子：
4.8
通讯作者：
Chimini, G
中科院分区：
文献类型：
--
作者：
Chambenoit, O;Hamon, Y;Chimini, G
作为丹吉尔病的分子基础的ABCA 1缺陷的鉴定突出了其在新生载脂蛋白颗粒的磷脂和胆固醇负载中的关键作用。事实上，ABCA 1的表达影响载脂蛋白A-I（apoA-I）介导的脂质从细胞膜的去除，并且最近已经提出ABCA 1作为apoA-I表面受体的可能作用。在本研究中，我们通过分析一组表达ABCA 1的功能或突变形式的转染子，研究了ABCA 1转运蛋白作为apoA-I受体的作用，我们提供的实验证据表明，一个功能ABCA 1转运蛋白的强制表达赋予apoA-I结合的表面能力。然而，这似乎依赖于ABCA 1功能。结构完整但ATP酶缺陷形式的转运蛋白不能引起配体的特异性细胞缔合，此外，膜缔合的apoA-I的扩散参数表明与膜脂质而不是蛋白质的相互作用。这些结果不支持ABCA 1和apoA-I之间的直接分子相互作用，而是表明，ABCA 1诱导的修饰的脂质分布在膜中，证明了磷脂酰丝氨酸exofacial flopping，产生一个生物物理微环境所需的apoA-I在细胞表面的对接。
The identification of defects in ABCA1 as the molecular basis of Tangier disease has highlighted its crucial role in the loading with phospholipids and cholesterol of nascent apolipoprotein particles. Indeed the expression of ABCA1 affects apolipoprotein A-I (apoA-I)-mediated removal of lipids from cell membranes, and the possible role of ABCA1 as an apoA-I surface receptor has been recently suggested, In the present study, we have investigated the role of the ABCA1 transporter as an apoA-I receptor with the analysis of a panel of transfectants expressing functional or mutant forms of ABCA1, We provide experimental evidence that the forced expression of a functional ABCA1 transporter confers surface competence for apoA-I binding. This, however, appears to be dependent on ABCA1 function. Structurally intact but ATPase-deficient forms of the transporter fail to elicit a specific cell association of the ligand, In addition the diffusion parameters of membrane-associated apoA-I indicate an interaction with membrane lipids rather than proteins. These results do not support a direct molecular interaction between ABCA1 and apoA-I, but rather suggest that the ABCA1-induced modification of the lipid distribution in the membrane, evidenced by the phosphatidylserine exofacial flopping, generates a biophysical microenvironment required for the docking of apoA-I at the cell surface.