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

  1. Nicolas Macaisne
  2. Laura Bellutti
  3. Kimberley Laband
  4. Frances Edwards
  5. Laras Pitayu-Nugroho
  6. Alison Gervais
  7. Thadshagine Ganeswaran
  8. Hélène Geoffroy
  9. Gilliane Maton
  10. Julie C Canman
  11. Benjamin Lacroix  Is a corresponding author
  12. Julien Dumont  Is a corresponding author
  1. Institut Jacques Monod, France
  2. Columbia University, United States
  3. 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

  1. Nicolas Macaisne

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0109-9845
  2. Laura Bellutti

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Kimberley Laband

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8535-2050
  4. Frances Edwards

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Laras Pitayu-Nugroho

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Alison Gervais

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Thadshagine Ganeswaran

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4986-4419
  8. Hélène Geoffroy

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3231-8369
  9. Gilliane Maton

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Julie C Canman

    Department of Pathology and Cell, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Benjamin Lacroix

    Centre de Recherche en Biologie Cellulaire de Montpellier, Montpellier, France
    For correspondence
    benjamin.lacroix@crbm.cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.
  12. Julien Dumont

    Institut Jacques Monod, Paris, France
    For correspondence
    julien.dumont@ijm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5312-9770

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.

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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  1. Nicolas Macaisne
  2. Laura Bellutti
  3. Kimberley Laband
  4. Frances Edwards
  5. Laras Pitayu-Nugroho
  6. Alison Gervais
  7. Thadshagine Ganeswaran
  8. Hélène Geoffroy
  9. Gilliane Maton
  10. Julie C Canman
  11. Benjamin Lacroix
  12. Julien Dumont
(2023)
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

Share this article

https://doi.org/10.7554/eLife.82579

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