Synergistic stabilization of microtubules by BUB-1, HCP-1 and CLS-2 controls microtubule pausing and meiotic spindle assembly
- Institut Jacques Monod, France
- Columbia University, United States
- Centre de Recherche en Biologie Cellulaire de Montpellier, France
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 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files; Source Data files have been provided for all figures.
Article and author information
Author details
Thadshagine Ganeswaran
Funding
Agence Nationale de la Recherche (ANR-19-CE13-0015)
- Nicolas Macaisne
Fondation pour la Recherche Médicale (Post Doctoral Fellowship)
- Laura Bellutti
European Research Council (CoG Chromosome 819179)
- Julien Dumont
Agence Nationale de la Recherche (ANR-19-CE13-0015)
- Julien Dumont
National Institutes of Health (R01GM117407)
- Julie C Canman
National Institutes of Health (R01GM130764)
- Julie C Canman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Thomas Surrey, Centre for Genomic Regulation (CRG), Spain
Version history
- Received: August 9, 2022
- Preprint posted: August 25, 2022 (view preprint)
- Accepted: February 16, 2023
- Accepted Manuscript published: February 17, 2023 (version 1)
- Version of Record published: March 10, 2023 (version 2)
Copyright
© 2023, Macaisne et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Synergistic stabilization of microtubules by BUB-1, HCP-1 and CLS-2 controls microtubule pausing and meiotic spindle assembly
eLife 12:e82579.
https://doi.org/10.7554/eLife.82579
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