Membrane cholesterol, lateral mobility, and the phosphatidylinositol 4,5-bisphosphate-dependent organization of cell actin
Membrane cholesterol, lateral mobility, and the phosphatidylinositol 4,5-bisphosphate-dependent organization of cell actin
复制标题
DOI：
10.1073/pnas.2336102100
复制
发表时间：
2003-11-25
影响因子：
11.1
通讯作者：
Edidin, M
中科院分区：
文献类型：
--
作者：
Kwik, J;Boyle, S;Edidin, M
对胆固醇耗竭的反应通常被认为是脂筏在细胞功能中发挥作用的证据。在这里，我们表明细胞胆固醇的耗尽对细胞和质膜的结构和功能具有全球性的影响。当细胞胆固醇慢性或急性耗尽时，膜蛋白的横向迁移率降低。流动性的变化是细胞肌动蛋白重组的结果。胆固醇耗竭后，磷脂酰肌醇4，5-二磷酸的GFP标记的Pleckstrin同源结构域与质膜的结合减少。这一结果表明，细胞骨架的重组依赖于质膜PI(4，5)P2的丢失或重新分布。与此观察一致的是，隔离质膜PI(4，5)P2的试剂模拟了胆固醇耗竭对肌动蛋白组织和侧向流动性的影响。
Responses to cholesterol depletion are often taken as evidence of a role for lipid rafts in cell function. Here, we show that depletion of cell cholesterol has global effects on cell and plasma membrane architecture and function. The lateral mobility of membrane proteins is reduced when cell cholesterol is chronically or acutely depleted. The change in mobility is a consequence of the reorganization of the cell actin. Binding of a GFP-tagged pleckstrin homology domain specific for phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] to the plasma membrane is reduced after cholesterol depletion. This result implies that the reorganization of cytoskeleton depends on the loss or redistribution of plasma membrane PI(4,5)P2. Consistent with this observation, agents that sequester plasma membrane PI(4,5)P2 mimic the effects of cholesterol depletion on actin organization and on lateral mobility.