Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA.
J Cell Biol. 2010 Dec 27;191(7):1239-49. doi: 10.1083/jcb.201006076. Epub 2010 Dec 20.
The metaphase spindle is a dynamic bipolar structure crucial for proper chromosome segregation, but how microtubules (MTs) are organized within the bipolar architecture remains controversial. To explore MT organization along the pole-to-pole axis, we simulated meiotic spindle assembly in two dimensions using dynamic MTs, a MT cross-linking force, and a kinesin-5-like motor. The bipolar structures that form consist of antiparallel fluxing MTs, but spindle pole formation requires the addition of a NuMA-like minus-end cross-linker and directed transport of MT depolymerization activity toward minus ends. Dynamic instability and minus-end depolymerization generate realistic MT lifetimes and a truncated exponential MT length distribution. Keeping the number of MTs in the simulation constant, we explored the influence of two different MT nucleation pathways on spindle organization. When nucleation occurs throughout the spindle, the simulation quantitatively reproduces features of meiotic spindles assembled in Xenopus egg extracts.
中期纺锤体是一个动态的双极结构,对于正确的染色体分离至关重要,但微管(MTs)在双极结构中的组织方式仍存在争议。为了探索沿着极对极轴的 MT 组织,我们使用动态 MTs、MT 交联力和类似于驱动蛋白-5 的马达在二维空间中模拟了减数分裂纺锤体的组装。形成的双极结构由反平行的流动 MTs 组成,但纺锤体极的形成需要添加类似于 NuMA 的负端交联器,并将 MT 解聚活性定向运输到负端。动态不稳定性和负端解聚产生了现实的 MT 寿命和截断的指数 MT 长度分布。在模拟中保持 MT 的数量不变,我们探索了两种不同的 MT 成核途径对纺锤体组织的影响。当核发生在整个纺锤体中时,模拟定量再现了在爪蟾卵提取物中组装的减数分裂纺锤体的特征。