Tuning lipid mixtures to induce or suppress domain formation across leaflets of unsupported asymmetric bilayers

Tuning lipid mixtures to induce or suppress domain formation across leaflets of unsupported asymmetric bilayers
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DOI:
10.1073/pnas.0702970105
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发表时间:
2008-01-08
影响因子:
11.1
通讯作者:
Keller, Sarah L.
Keller, Sarah L.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Collins, Marcus D.;Keller, Sarah L.

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细胞质膜的脂质和蛋白质组成都是不对称的。在信号传导过程中,膜两侧的蛋白质共定位的机制尚不清楚,但可能是由于外叶诱导内叶结构域所致。在这里,我们表明,液体域形成在不对称的Montal-Mueller平面双层膜中,其中一个叶让的组合物将相分离的对称双层和其他的不会。同样重要的是,通过调整第二小叶的脂质组成,我们能够抑制第一小叶中的结构域。当结构域存在于不对称膜中时,每个小叶包含三种不同脂质成分的区域,这意味着强烈的叶间相互作用。我们的研究结果表明,结构域之间的诱导机制的细胞质膜的外部和内部小叶不一定需要膜蛋白的参与。基于这些发现,我们提出了细胞可以通过调节局部脂质组成或叶间相互作用来积极调节蛋白质功能的机制。
Plasma membranes of cells are asymmetric in both lipid and protein composition. The mechanism by which proteins on both sides of the membrane colocalize during signaling events is unknown but may be due to the induction of inner leaflet domains by the outer leaflet. Here we show that liquid domains form in asymmetric Montal-Mueller planar bilayers in which one leaf let's composition would phase-separate in a symmetric bilayer and the other's would not. Equally important, by tuning the lipid composition of the second leaf let, we are able to suppress domains in the first leaflet. When domains are present in asymmetric membranes, each leaflet contains regions of three distinct lipid compositions, implying strong interleaf let interactions. Our results show that mechanisms of domain induction between the outer and inner leaflets of cell plasma membranes do not necessarily require the participation of membrane proteins. Based on these findings, we suggest mechanisms by which cells could actively regulate protein function by modulating local lipid composition or interleaf let interactions.