Greasing Their Way: Lipid Modifications Determine Protein Association with Membrane Rafts
Greasing Their Way: Lipid Modifications Determine Protein Association with Membrane Rafts
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DOI：
10.1021/bi100882y
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发表时间：
2010-08-03
期刊：
影响因子：
2.9
通讯作者：
Simons, Kai
中科院分区：
文献类型：
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作者：
Levental, Ilya;Grzybek, Michal;Simons, Kai
越来越多的证据表明，生物膜可以横向细分为富含特定脂质和蛋白质成分的域，这些域可能参与调节一些重要的细胞过程。一个例子是膜筏，其是依赖于固醇和鞘脂之间的优先缔合的脂质介导的结构域，并且包括膜蛋白的特定子集。虽然筏的脂质和蛋白质组成已被广泛的特点，决定蛋白质分配到这些领域的结构细节仍然没有得到解决。在这里，我们回顾的证据表明，翻译后修饰饱和脂质招募外周和跨膜蛋白筏，而短，不饱和，和/或支链烃链防止筏协会。研究最广泛的一组筏相关蛋白是糖磷脂酰肌醇锚定蛋白（GPI-AP），我们回顾了各种证据支持筏协会这些饱和的脂质锚定的细胞外外周蛋白。对于跨膜和细胞内外周蛋白，S-酰化与饱和脂肪酸介导筏分区，这种修饰的动态性质提出了一个令人兴奋的可能性，酶调节筏协会。其他常见的脂质修饰，即异戊二烯化和肉豆蔻酰化，讨论了其可能的作用，在靶向蛋白质的nonraft膜区域。最后，尽管筏亲和力和脂质修饰之间的关联已得到充分表征，但我们讨论了有关这些翻译后修饰的调节和重塑及其在膜结构域跨双层偶联中的作用的几个悬而未决的问题。
Increasing evidence suggests that biological membranes can be laterally subdivided into domains enriched in specific lipid and protein components and that these domains may be involved in the regulation of a number of vital cellular processes. An example is membrane rafts, which are lipid-mediated domains dependent on preferential association between sterols and sphingolipids and inclusive of a specific subset of membrane proteins. While the lipid and protein composition of rafts has been extensively characterized, the structural details determining protein partitioning to these domains remain unresolved. Here, we review evidence suggesting that post-translation modification by saturated lipids recruits both peripheral and transmembrane proteins to rafts, while short, unsaturated, and/or branched hydrocarbon chains prevent raft association. The most widely studied group of raft-associated proteins are glycophosphatidylinositolanchored proteins (GPI-AP), and we review a variety of evidence supporting raft-association of these saturated lipid-anchored extracellular peripheral proteins. For transmembrane and intracellular peripheral proteins, S-acylation with saturated fatty acids mediates raft partitioning, and the dynamic nature of this modification presents an exciting possibility of enzymatically regulated raft association. The other common lipid modifications, that is, prenylation and myristoylation, are discussed in light of their likely role in targeting proteins to nonraft membrane regions. Finally, although the association between raft affinity and lipid modification is well-characterized, we discuss several open questions regarding regulation and remodeling of these post-translational modifications as well as their role in transbilayer coupling of membrane domains.