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Force-transducing molecular ensembles at growing microtubule tips control mitotic spindle size

Author

Listed:
  • Lee-Ya Chu

    (The Francis Crick Institute)

  • Daniel Stedman

    (The Francis Crick Institute
    King’s College London)

  • Julian Gannon

    (The Francis Crick Institute)

  • Susan Cox

    (King’s College London)

  • Georgii Pobegalov

    (The Francis Crick Institute
    University College London)

  • Maxim I. Molodtsov

    (The Francis Crick Institute
    University College London)

Abstract

Correct mitotic spindle size is required for accurate chromosome segregation during cell division. It is controlled by mechanical forces generated by molecular motors and non-motor proteins acting on spindle microtubules. However, how forces generated by individual proteins enable bipolar spindle organization is not well understood. Here, we develop tools to measure contributions of individual molecules to this force balance. We show that microtubule plus-end binding proteins act at microtubule tips synergistically with minus-end directed motors to produce a system that can generate both pushing and pulling forces. To generate pushing force, the system harnesses forces generated by the growing tips of microtubules providing unique contribution to the force balance distinct from all other motors that act in the mitotic spindle. Our results reveal that microtubules are essential force generators for establishing spindle size and pave the way for understanding how mechanical forces can be fine-tuned to control the fidelity of chromosome segregation.

Suggested Citation

  • Lee-Ya Chu & Daniel Stedman & Julian Gannon & Susan Cox & Georgii Pobegalov & Maxim I. Molodtsov, 2024. "Force-transducing molecular ensembles at growing microtubule tips control mitotic spindle size," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54123-2
    DOI: 10.1038/s41467-024-54123-2
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    References listed on IDEAS

    as
    1. Annemarie Lüdecke & Anja-Maria Seidel & Marcus Braun & Zdenek Lansky & Stefan Diez, 2018. "Diffusive tail anchorage determines velocity and force produced by kinesin-14 between crosslinked microtubules," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    2. Bungo Akiyoshi & Krishna K. Sarangapani & Andrew F. Powers & Christian R. Nelson & Steve L. Reichow & Hugo Arellano-Santoyo & Tamir Gonen & Jeffrey A. Ranish & Charles L. Asbury & Sue Biggins, 2010. "Tension directly stabilizes reconstituted kinetochore-microtubule attachments," Nature, Nature, vol. 468(7323), pages 576-579, November.
    3. Stephen R. Norris & Seungyeon Jung & Prashant Singh & Claire E. Strothman & Amanda L. Erwin & Melanie D. Ohi & Marija Zanic & Ryoma Ohi, 2018. "Microtubule minus-end aster organization is driven by processive HSET-tubulin clusters," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

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