ATP-binding cassette transporter A1 expression disrupts raft membrane microdomains through its ATPase-related functions
ATP-binding cassette transporter A1 expression disrupts raft membrane microdomains through its ATPase-related functions
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DOI：
10.1074/jbc.m602247200
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发表时间：
2006-11-24
影响因子：
4.8
通讯作者：
Zha, Xiaohui
中科院分区：
文献类型：
--
作者：
Landry, Yves D.;Denis, Maxime;Zha, Xiaohui
已知ATP结合盒转运蛋白A1（ABCA 1）介导胆固醇流出至贫脂载脂蛋白A-I。此外，ABCA 1已被证明影响质膜的功能，如内吞作用和吞噬作用。在这里，我们报告ABCA 1的表达结果在一个显着的重新分配的胆固醇和鞘磷脂从筏非筏。小窝蛋白，筏/小窝标记物也重新分配从点状小窝样结构的质膜的一般区域后ABCA 1的表达。此外，我们观察到ABCA 1表达细胞中Akt活化的显著减少，与筏破坏一致。然而，细胞膜中的胆固醇含量没有改变。此外，我们提供的证据表明，一个非功能性ABCA 1突变的ATP结合域，A937 V，未能重新分配胆固醇，鞘磷脂，或小窝。A937 V也不能影响Akt激活。最后，我们表明，载脂蛋白A-I优先与非筏膜ABCA 1表达细胞。因此，我们的结果表明，ABCA 1可能通过其ATP酶相关功能引起质膜整体脂质包装的变化。ABCA 1的这种重组有效地扩展了非筏膜部分，因此，预先调节细胞的胆固醇流出。
ATP-binding cassette transporter A1(ABCA1) is known to mediate cholesterol efflux to lipid-poor apolipoprotein A-I. In addition, ABCA1 has been shown to influence functions of the plasma membrane, such as endocytosis and phagocytosis. Here, we report that ABCA1 expression results in a significant redistribution of cholesterol and sphingomyelin from rafts to non-rafts. Caveolin, a raft/caveolae marker also redistributes from punctate caveolae-like structures to the general area of the plasma membrane upon ABCA1 expression. Furthermore, we observed significant reduction of Akt activation in ABCA1-expressing cells, consistent with raft disruption. Cholesterol content in the plasma membrane is, however, notaltered. Moreover, we provide evidence that a non-functional ABCA1 with mutation in an ATP-binding domain, A937V, fails to redistribute cholesterol, sphingomyelin, or caveolin. A937V also fails to influence Akt activation. Finally, we show that apolipoprotein A-I preferentially associates with non-raft membranes in ABCA1-expressing cells. Our results thus demonstrate that ABCA1 causes a change in overall lipid packing of the plasma membrane, likely through its ATPase-related functions. Such reorganization by ABCA1 effectively expands the non-raft membrane fractions and, consequentially, pre-conditions cells for cholesterol efflux.