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BUB-1、HCP-1 和 CLS-2 通过协同稳定微管控制微管停顿和减数分裂纺锤体的组装。

Synergistic stabilization of microtubules by BUB-1, HCP-1, and CLS-2 controls microtubule pausing and meiotic spindle assembly.

机构信息

Université Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, France.

Columbia University; Department of Pathology and Cell Biology, New York, United States.

出版信息

Elife. 2023 Feb 17;12:e82579. doi: 10.7554/eLife.82579.

DOI:10.7554/eLife.82579
PMID:36799894
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10005782/
Abstract

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 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.

摘要

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的。纺锤体微管与动粒的相互作用对于染色体的双定向至关重要。最初是动态的，以允许纺锤体组装和动粒附着，这对于染色体对齐是必不可少的，微管最终被稳定下来，以分别在有丝分裂和减数分裂 I 中有效地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期间，微管动力学的精确控制至关重要。在这里，我们研究了一个动粒模块的组装和作用，该模块由激酶 BUB-1、两个冗余的 CENP-F 同源物 HCP-1/2 和 CLASP 家族成员 CLS-2（以下简称 BHC 模块）组成，该模块在控制卵母细胞中的微管动力学。我们使用 BHC 成分的体内结构功能分析和体外基于微管的测定的组合，表明 BHC 成分稳定微管，这对于减数分裂纺锤体形成和准确的染色体分离是必不可少的。总的来说，我们的结果表明，BUB-1 和 HCP-1/2 不仅作为 CLS-2 在动粒上的靶向成分，而且通过促进微管暂停协同控制动粒-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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/acbc0a65325a/elife-82579-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/82d3795cc30c/elife-82579-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/f5a15c0f2728/elife-82579-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/307660e52b62/elife-82579-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/8bb6d974ec92/elife-82579-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/acbc0a65325a/elife-82579-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/82d3795cc30c/elife-82579-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/8556116c1791/elife-82579-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/9a32910291dd/elife-82579-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/9399180900ab/elife-82579-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/a6ea69689499/elife-82579-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/8ab36887df62/elife-82579-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/e753892fcf56/elife-82579-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/2db4f02c4069/elife-82579-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/860cbec19960/elife-82579-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/aa7565eea88b/elife-82579-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/f5a15c0f2728/elife-82579-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/307660e52b62/elife-82579-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/8bb6d974ec92/elife-82579-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6f/10005782/acbc0a65325a/elife-82579-fig6-figsupp1.jpg

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Functional midbody assembly in the absence of a central spindle.
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