Molecular determinants of the Ska-Ndc80 interaction and their influence on microtubule tracking and force-coupling

  1. Pim J Huis in 't Veld
  2. Vladimir A Volkov
  3. Isabelle D Stender
  4. Andrea Musacchio  Is a corresponding author
  5. Marileen Dogterom  Is a corresponding author
  1. Max Planck Institute of Molecular Physiology, Germany
  2. Delft University of Technology, Netherlands

Abstract

Errorless chromosome segregation requires load-bearing attachments of the plus ends of spindle microtubules to chromosome structures named kinetochores. How these end-on kinetochore attachments are established following initial lateral contacts with the microtubule lattice is poorly understood. Two microtubule-binding complexes, the Ndc80 and Ska complexes, are important for efficient end-on coupling and may function as a unit in this process, but precise conditions for their interaction are unknown. Here, we report that the Ska-Ndc80 interaction is phosphorylation-dependent and does not require microtubules, applied force, or several previously identified functional determinants including the Ndc80-loop and the Ndc80-tail. Both the Ndc80-tail, which we reveal to be essential for microtubule end-tracking, and Ndc80-bound Ska stabilize microtubule ends in a stalled conformation. Modulation of force-coupling efficiency demonstrates that the duration of stalled microtubule disassembly predicts whether a microtubule is stabilized and rescued by the kinetochore, likely reflecting a structural transition of the microtubule end.

Data availability

All relevant data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

Article and author information

Author details

  1. Pim J Huis in 't Veld

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0234-6390
  2. Vladimir A Volkov

    Department of Bionanoscience, Delft University of Technology, Delft, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5407-3366
  3. Isabelle D Stender

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Andrea Musacchio

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    For correspondence
    andrea.musacchio@mpi-dortmund.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2362-8784
  5. Marileen Dogterom

    Department of Bionanoscience, Delft University of Technology, Delft, Netherlands
    For correspondence
    m.dogterom@tudelft.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8803-5261

Funding

European Commission (ERC AdG RECEPIANCE (proposal 669686))

  • Andrea Musacchio

Deutsche Forschungsgemeinschaft (CRC1093)

  • Andrea Musacchio

European Commission (ERC SG MODELCELL (proposal 609822))

  • Marileen Dogterom

European Molecular Biology Organization (STF7203)

  • Pim J Huis in 't Veld

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Andrew D McAinsh, University of Warwick, United Kingdom

Version history

  1. Received: June 20, 2019
  2. Accepted: November 26, 2019
  3. Accepted Manuscript published: December 5, 2019 (version 1)
  4. Version of Record published: December 23, 2019 (version 2)

Copyright

© 2019, Huis in 't Veld 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. Pim J Huis in 't Veld
  2. Vladimir A Volkov
  3. Isabelle D Stender
  4. Andrea Musacchio
  5. Marileen Dogterom
(2019)
Molecular determinants of the Ska-Ndc80 interaction and their influence on microtubule tracking and force-coupling
eLife 8:e49539.
https://doi.org/10.7554/eLife.49539

Share this article

https://doi.org/10.7554/eLife.49539

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    Fetal growth restriction (FGR) is a pregnancy complication in which a newborn fails to achieve its growth potential, increasing the risk of perinatal morbidity and mortality. Chronic maternal gestational hypoxia, as well as placental insufficiency are associated with increased FGR incidence; however, the molecular mechanisms underlying FGR remain unknown.

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    Funding:

    This work was supported by the Weizmann Krenter Foundation and the Weizmann – Ichilov (Tel Aviv Sourasky Medical Center) Collaborative Grant in Biomedical Research, by the Minerva Foundation, by the ISF KillCorona grant 3777/19.