Synergistic stabilization of microtubules by BUB-1, HCP-1, and CLS-2 controls microtubule pausing and meiotic spindle assembly.
Synergistic stabilization of microtubules by BUB-1, HCP-1, and CLS-2 controls microtubule pausing and meiotic spindle assembly.
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DOI：
10.7554/elife.82579
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发表时间：
2023-02-17
期刊：
影响因子：
7.7
通讯作者：
Dumont J
中科院分区：
文献类型：
--
作者：
Macaisne N;Bellutti L;Laband K;Edwards F;Pitayu-Nugroho L;Gervais A;Ganeswaran T;Geoffroy H;Maton G;Canman JC;Lacroix B;Dumont J
在细胞分裂过程中，染色体分离是由基于微管的纺锤体协调进行的。纺锤体微管和着丝点之间的相互作用是染色体双向的中心。微管最初是动态的，允许纺锤体组装和动粒附着，这对染色体配对是必不可少的，最终微管稳定下来，以便在有丝分裂和减数分裂I期间分别有效分离姐妹染色单体和同源染色体。因此，在有丝分裂和减数分裂过程中，对微管动力学的精确控制是至关重要的。在这里，我们研究了动粒模块的组装和在线虫卵母细胞微管动力学中的作用。动粒模块由激酶bub-1、两个冗余的CENP-F同源基因hcp-1/2和CLASP家族成员CLS-2(以下称为BHC模块)组成。结合体内BHC组分的结构功能分析和体外基于微管的分析，我们发现BHC组分稳定了微管，这对于减数分裂纺锤体的形成和准确的染色体分离是必不可少的。总体而言，我们的结果表明，bub-1和hcp-1/2不仅在运动中心作为CLS-2的靶向成分，而且通过促进微管停顿来协同控制动粒-微管动力学。总之，我们的结果表明，BUB-1和Hcp-1/2在完整的BHC模块的背景下积极参与动粒-微管动力学的控制，以促进减数分裂中的纺锤体组装和准确的染色体分离。
During cell division, chromosome segregation is orchestrated by a microtubule-based spindle. Interaction between spindle microtubules and kinetochores is central to the bi-orientation of chromosomes. Initially dynamic to allow spindle assembly and kinetochore attachments, which is essential for chromosome alignment, microtubules are eventually stabilized for efficient segregation of sister chromatids and homologous chromosomes during mitosis and meiosis I, respectively. Therefore, the precise control of microtubule dynamics is of utmost importance during mitosis and meiosis. Here, we study the assembly and role of a kinetochore module, comprised of the kinase BUB-1, the two redundant CENP-F orthologs HCP-1/2, and the CLASP family member CLS-2 (hereafter termed the BHC module), in the control of microtubule dynamics in Caenorhabditis elegans oocytes. Using a combination of in vivo structure-function analyses of BHC components and in vitro microtubule-based assays, we show that BHC components stabilize microtubules, which is essential for meiotic spindle formation and accurate chromosome segregation. Overall, our results show that BUB-1 and HCP-1/2 do not only act as targeting components for CLS-2 at kinetochores, but also synergistically control kinetochore-microtubule dynamics by promoting microtubule pause. Together, our results suggest that BUB-1 and HCP-1/2 actively participate in the control of kinetochore-microtubule dynamics in the context of an intact BHC module to promote spindle assembly and accurate chromosome segregation in meiosis.
Xorbit/clasp将动态微管连接到爪蟾减少纺锤体中的染色体。
影响因子：
7.8
作者：
Hannak, Eva;Heald, Rebecca
通讯作者：
Heald, Rebecca
影响因子：
4.5
作者：
Davis-Roca AC;Divekar NS;Ng RK;Wignall SM
通讯作者：
Wignall SM