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Evidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules

Author

Listed:
  • Cédric Castrogiovanni

    (University of Geneva
    University of Geneva)

  • Alessio V. Inchingolo

    (University of Warwick
    University of Warwick)

  • Jonathan U. Harrison

    (University of Warwick
    University of Warwick)

  • Damian Dudka

    (University of Geneva
    University of Geneva
    University of Pennsylvania)

  • Onur Sen

    (University of Warwick
    University of Warwick)

  • Nigel J. Burroughs

    (University of Warwick
    University of Warwick)

  • Andrew D. McAinsh

    (University of Warwick
    University of Warwick)

  • Patrick Meraldi

    (University of Geneva
    University of Geneva)

Abstract

Current models infer that the microtubule-based mitotic spindle is built from GDP-tubulin with small GTP caps at microtubule plus-ends, including those that attach to kinetochores, forming the kinetochore-fibres. Here we reveal that kinetochore-fibres additionally contain a dynamic mixed-nucleotide zone that reaches several microns in length. This zone becomes visible in cells expressing fluorescently labelled end-binding proteins, a known marker for GTP-tubulin, and endogenously-labelled HURP - a protein which we show to preferentially bind the GDP microtubule lattice in vitro and in vivo. We find that in mitotic cells HURP accumulates on the kinetochore-proximal region of depolymerising kinetochore-fibres, whilst avoiding recruitment to nascent polymerising K-fibres, giving rise to a growing “HURP-gap”. The absence of end-binding proteins in the HURP-gaps leads us to postulate that they reflect a mixed-nucleotide zone. We generate a minimal quantitative model based on the preferential binding of HURP to GDP-tubulin to show that such a mixed-nucleotide zone is sufficient to recapitulate the observed in vivo dynamics of HURP-gaps.

Suggested Citation

  • Cédric Castrogiovanni & Alessio V. Inchingolo & Jonathan U. Harrison & Damian Dudka & Onur Sen & Nigel J. Burroughs & Andrew D. McAinsh & Patrick Meraldi, 2022. "Evidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32421-x
    DOI: 10.1038/s41467-022-32421-x
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    References listed on IDEAS

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    1. Jonathan W Armond & Edward F Harry & Andrew D McAinsh & Nigel J Burroughs, 2015. "Inferring the Forces Controlling Metaphase Kinetochore Oscillations by Reverse Engineering System Dynamics," PLOS Computational Biology, Public Library of Science, vol. 11(11), pages 1-26, November.
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    Cited by:

    1. Venecia Alexandria Valdez & Meisheng Ma & Bernardo Gouveia & Rui Zhang & Sabine Petry, 2024. "HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Athira Saju & Po-Pang Chen & Tzu-Han Weng & Su-Yi Tsai & Akihiro Tanaka & Yu-Ting Tseng & Chih-Chia Chang & Chun-Hsiung Wang & Yuta Shimamoto & Kuo-Chiang Hsia, 2024. "HURP binding to the vinca domain of β-tubulin accounts for cancer drug resistance," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Juan M. Perez-Bertoldi & Yuanchang Zhao & Akanksha Thawani & Ahmet Yildiz & Eva Nogales, 2024. "HURP regulates Kif18A recruitment and activity to synergistically control microtubule dynamics," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Hugo Girão & Joana Macário-Monteiro & Ana C. Figueiredo & Ricardo Silva e Sousa & Elena Doria & Vladimir Demidov & Hugo Osório & Ariana Jacome & Patrick Meraldi & Ekaterina L. Grishchuk & Helder Maiat, 2024. "α-tubulin detyrosination fine-tunes kinetochore-microtubule attachments," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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