Role of spatial patterns and kinetochore architecture in spindle morphogenesis.

Role of spatial patterns and kinetochore architecture in spindle morphogenesis.
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空间模式和动粒结构在纺锤体形态发生中的作用。

DOI:
10.1016/j.semcdb.2021.03.016
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发表时间:
2021-09
影响因子:
7.3
通讯作者:
Khodjakov A
Khodjakov A
中科院分区:
生物学2区
文献类型:
--
作者:
Renda F;Khodjakov A

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有丝分裂纺锤体是一种自我组装的大分子机器,负责细胞分裂过程中染色体的忠实分离。纺锤体的组装被认为是由“搜索和捕获”(S&C)原理控制的,其中动态微管探索空间以寻找动粒,而后者捕获微管,从而将染色体连接到纺锤体。由于着丝粒和微管之间的遭遇的随机性,将所有染色体整合到纺锤体中所需的时间受到几何约束的深刻影响,例如着丝粒的大小和形状以及它们在纺锤体组装开始时在空间中的分布。近年来,已经发现了控制这些参数的几种分子机制。现在很清楚,随机S&C发生在结构化空间中,其中组件被优化分布和定向以最小化空间障碍。许多非中心体微管附近的着丝粒加速捕获成核,而在着丝粒结构的变化,在不同阶段的纺锤体组装促进正确的连接的姐妹着丝粒到相反的纺锤体极。在这里,我们讨论如何协调行动的多个促进机制,确保主轴组装迅速,但错误的数量最少。
Mitotic spindle is a self-assembling macromolecular machine responsible for the faithful segregation of chromosomes during cell division. Assembly of the spindle is believed to be governed by the ‘Search & Capture’ (S&C) principle in which dynamic microtubules explore space in search of kinetochores while the latter capture microtubules and thus connect chromosomes to the spindle. Due to the stochastic nature of the encounters between kinetochores and microtubules, the time required for incorporating all chromosomes into the spindle is profoundly affected by geometric constraints, such as the size and shape of kinetochores as well as their distribution in space at the onset of spindle assembly. In recent years, several molecular mechanisms that control these parameters have been discovered. It is now clear that stochastic S&C takes place in structured space, where components are optimally distributed and oriented to minimize steric hindrances. Nucleation of numerous non-centrosomal microtubules near kinetochores accelerates capture, while changes in the kinetochore architecture at various stages of spindle assembly promote proper connection of sister kinetochores to the opposite spindle poles. Here we discuss how the concerted action of multiple facilitating mechanisms ensure that the spindle assembles rapidly yet with a minimal number of errors.
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