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系列综述——微管生长动力学及其数值模拟 Day 6

上接Day 5
本系列章节、图表、引文均连续编号。

3. 微管动态特性的研究现状

注:今日内容为第三部分的引言。


微管的动态性质对于微管行使自身的功能至关重要 (85-87)。尽管一系列有形和无形的因素,如化合物和细胞内信号,会调控微管的动态行为 (88),帮助其变形,集束,运动等,有两类动态特性却是微管内秉的,可以在纯净的微管蛋白溶液中发生:一为踏车现象,另一为动态不稳定。由于微管主体是紧实的晶格结构,一般认为亚基的添加和移除只能通过端部发生,以上两种动态行为就均与微管端部的加、解聚相关。

环境中亚基的浓度会影响微管的组装,如果高于临界浓度则微管倾向于加聚,反之则解聚。微管的极性结构导致正端有着比负端更强的动态性,两端的临界浓度不同,若周围环境恰好使正端加聚而负端解聚,且两者速率相等,则表面上看,微管的长度并没有发生变化,亚基仿佛从正端流向了负端,这就是踏车现象 (89-93)。踏车并不需要任何的外在驱动,另一细胞骨架纤维——肌动蛋白丝也发生踏车。

动态不稳定性是指微管不停地在生长和收缩间随机地转换,长度不断发生着变化 (94-96),如图11所示 (2),从加聚状态突然转为解聚状态称为“灾变”,而从解聚转为加聚则称为“拯救”。“灾变”和“拯救”的发生都是随机的,一般可以用四个参数来刻画动态不稳定性的平均过程——生长速率,收缩速率,灾变频率,和拯救频率。这几个参数间是解耦的,即使一根微管上非常频繁地发生着灾变,其依然可以生长地很快。值得注意的是,虽然快速的动态行为对许多细胞至关重要,比如有丝分裂中期就是依靠微管的不断伸长和收缩来捕获染色体,但在一些不能复制的细胞,如神经元中,微管却是基本保持静止的,此时结构如果去组装将导致神经变性,引发阿兹海默症等疾病;在这些情况下,微管的稳定是重中之重。

图11微管的动态不稳定性:蓝线:生长段;红线:收缩段 (2)

微管的正端和负端都能体现出动态不稳定性,不过它们的生长和收缩速率、灾变和拯救频率各不相同 (96)。一般的,正端生长更快,灾变也更频繁 (13);在体内,则两端的动态性差别更显著,负端在一些结合蛋白的作用下基本保持稳定 (97)。大多数动态不稳定性的研究都着眼于正端。

参考文献:

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