Identifying optimal lipid raft characteristics required to promote nanoscale protein-protein interactions on the plasma membrane
Identifying optimal lipid raft characteristics required to promote nanoscale protein-protein interactions on the plasma membrane
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DOI：
10.1128/mcb.26.1.313-323.2006
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发表时间：
2006-01-01
影响因子：
5.3
通讯作者：
Hancock, JF
中科院分区：
文献类型：
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作者：
Nicolau, DV;Burrage, K;Hancock, JF
信号蛋白进入微区的动态横向分离被提出以促进信号转导，但可能实现此功能的微区尺寸、流动性和扩散的限制尚未确定。在这里，我们询问质膜的随机空间模型，以确定微区如何影响蛋白质动力学。以脂筏为代表的微区，我们表明，减少蛋白质的流动性筏隔离动态分区蛋白质，但平衡浓度在很大程度上是独立的筏的大小和流动性。筏弱阻碍小规模的蛋白质扩散，但更强烈地阻碍长距离的蛋白质流动性。然而，筏分配和筏排除蛋白质的长程流动性降低到类似的程度。动态分割成筏增加了特定的蛋白质间碰撞率，但为了最大限度地发挥这一关键的生物相关功能，筏必须小（直径，6至14 nm）和移动的。分子间碰撞也可以通过筏选择性捕获和排斥蛋白质来促进，尽管这种机制通常不如简单的动态分配有效。概括这些结果，我们得出结论，微区可以很容易地作为蛋白质浓缩器或隔离器，但似乎有显着的限制，如果微区的大小和流动性也需要作为反应室，促进纳米级蛋白质-蛋白质相互作用。这些结果可能有显着的影响，许多信号级联的支架或组装在质膜微区。
The dynamic lateral segregation of signaling proteins into microdomains is proposed to facilitate signal transduction, but the constraints on microdomain size, mobility, and diffusion that might realize this function are undefined. Here we interrogate a stochastic spatial model of the plasma membrane to determine how microdomains affect protein dynamics. Taking lipid rafts as representative microdomains, we show that reduced protein mobility in rafts segregates dynamically partitioning proteins, but the equilibrium concentration is largely independent of raft size and mobility. Rafts weakly impede small-scale protein diffusion but more strongly impede long-range protein mobility. The long-range mobility of raft-partitioning and raft-excluded proteins, however, is reduced to a similar extent. Dynamic partitioning into rafts increases specific interprotein collision rates, but to maximize this critical, biologically relevant function, rafts must be small (diameter, 6 to 14 nm) and mobile. Intermolecular collisions can also be favored by the selective capture and exclusion of proteins by rafts, although this mechanism is generally less efficient than simple dynamic partitioning. Generalizing these results, we conclude that microdomains can readily operate as protein concentrators or isolators but there appear to be significant constraints on size and mobility if microdomains are also required to function as reaction chambers that facilitate nanoscale protein-protein interactions. These results may have significant implications for the many signaling cascades that are scaffolded or assembled in plasma membrane microdomains.