MRC Laboratory of Molecular Cell Biology and the IPLS, University College London, Gower Street, London, WC1E 6BT, UK.
BMC Biol. 2018 Jan 23;16(1):14. doi: 10.1186/s12915-017-0478-z.
Entry into mitosis triggers profound changes in cell shape and cytoskeletal organisation. Here, by studying microtubule remodelling in human flat mitotic cells, we identify a two-step process of interphase microtubule disassembly.
First, a microtubule-stabilising protein, Ensconsin/MAP7, is inactivated in prophase as a consequence of its phosphorylation downstream of Cdk1/cyclin B. This leads to a reduction in interphase microtubule stability that may help to fuel the growth of centrosomally nucleated microtubules. The peripheral interphase microtubules that remain are then rapidly lost as the concentration of tubulin heterodimers falls following dissolution of the nuclear compartment boundary. Finally, we show that a failure to destabilise microtubules in prophase leads to the formation of microtubule clumps, which interfere with spindle assembly.
This analysis highlights the importance of the step-wise remodelling of the microtubule cytoskeleton and the significance of permeabilisation of the nuclear envelope in coordinating the changes in cellular organisation and biochemistry that accompany mitotic entry.
进入有丝分裂会引发细胞形状和细胞骨架组织的深刻变化。在这里,通过研究人类平面有丝分裂细胞中的微管重塑,我们确定了有丝分裂前期微管解体的两步过程。
首先,作为 Cdk1/周期蛋白 B 下游磷酸化的结果,微管稳定蛋白 Ensconsin/MAP7 在前期失活。这导致有丝分裂前期微管稳定性降低,这可能有助于为中心体起源的微管生长提供动力。随着核区室边界溶解,微管二聚体浓度下降,剩下的外周有丝分裂前期微管迅速丢失。最后,我们表明,前期微管不能失稳会导致微管团块的形成,这会干扰纺锤体的组装。
该分析强调了微管细胞骨架的逐步重塑的重要性,以及核膜通透性在协调伴随有丝分裂进入的细胞组织和生化变化中的重要性。