European Molecular Biology Laboratory, Heidelberg, Germany.
PLoS One. 2007 Feb 28;2(2):e244. doi: 10.1371/journal.pone.0000244.
Assembly of the mitotic spindle is a classic example of macromolecular self-organization. During spindle assembly, microtubules (MTs) accumulate around chromatin. In centrosomal spindles, centrosomes at the spindle poles are the dominating source of MT production. However, many systems assemble anastral spindles, i.e., spindles without centrosomes at the poles. How anastral spindles produce and maintain a high concentration of MTs in the absence of centrosome-catalyzed MT production is unknown. With a combined biochemistry-computer simulation approach, we show that the concerted activity of three components can efficiently concentrate microtubules (MTs) at chromatin: (1) an external stimulus in form of a RanGTP gradient centered on chromatin, (2) a feed-back loop where MTs induce production of new MTs, and (3) continuous re-organization of MT structures by dynamic instability. The mechanism proposed here can generate and maintain a dissipative MT super-structure within a RanGTP gradient.
有丝分裂纺锤体的组装是一个典型的大分子自组织的例子。在纺锤体组装过程中,微管(MTs)在染色质周围积累。在中心体纺锤体中,纺锤体两极的中心体是 MT 产生的主要来源。然而,许多系统组装无中心体的星体纺锤体,即两极没有中心体的纺锤体。在没有中心体催化的 MT 产生的情况下,无中心体纺锤体如何产生和维持 MT 的高浓度尚不清楚。我们采用组合生物化学-计算机模拟的方法表明,三种成分的协同作用可以有效地将微管(MTs)集中在染色质上:(1)以染色质为中心的 RanGTP 梯度的外部刺激,(2)MT 诱导新的 MT 产生的反馈回路,以及(3)通过动态不稳定性对 MT 结构进行连续重组。这里提出的机制可以在 RanGTP 梯度内产生和维持耗散的 MT 超结构。