Lipid microdomains and the regulation of ion channel function
Lipid microdomains and the regulation of ion channel function
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DOI：
10.1113/jphysiol.2010.191585
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发表时间：
2010-09-01
影响因子：
5.5
通讯作者：
Dart, Caroline
中科院分区：
文献类型：
--
作者：
Dart, Caroline
许多类型的离子通道定位于被称为脂质微域或筏的质膜中富含胆固醇和鞘脂的区域。这些独特的脂质微环境的确切生理作用仍然难以捉摸，主要是由于研究这些潜在的极小和动态领域的困难。然而，越来越多的证据表明，膜筏以多种不同的方式调节通道功能。筏体富集的脂质，如胆固醇和鞘脂，通过直接的蛋白质-脂质相互作用或通过影响双分子层的物理性质，对通道活性产生影响。筏似乎也选择性地招募相互作用的信号分子来产生亚细胞区室，这可能对有效和选择性的信号转导很重要。与筏相关支架蛋白（如小窝蛋白）的直接相互作用也可以通过改变门控动力学或影响运输和表面表达来影响通道功能。因此，离子通道与膜内特定脂质微环境的选择性结合可能是通道生理学的一个重要和基本的调节方面。这篇简短的综述强调了一些现有的信道功能筏调制的证据。
Many types of ion channel localize to cholesterol and sphingolipid-enriched regions of the plasma membrane known as lipid microdomains or 'rafts'. The precise physiological role of these unique lipid microenvironments remains elusive due largely to difficulties associated with studying these potentially extremely small and dynamic domains. Nevertheless, increasing evidence suggests that membrane rafts regulate channel function in a number of different ways. Raft-enriched lipids such as cholesterol and sphingolipids exert effects on channel activity either through direct protein-lipid interactions or by influencing the physical properties of the bilayer. Rafts also appear to selectively recruit interacting signalling molecules to generate subcellular compartments that may be important for efficient and selective signal transduction. Direct interaction with raft-associated scaffold proteins such as caveolin can also influence channel function by altering gating kinetics or by affecting trafficking and surface expression. Selective association of ion channels with specific lipid microenvironments within the membrane is thus likely to be an important and fundamental regulatory aspect of channel physiology. This brief review highlights some of the existing evidence for raft modulation of channel function.