Human kinetochores are swivel joints that mediate microtubule attachments

  1. Chris A Smith
  2. Andrew D McAinsh  Is a corresponding author
  3. Nigel J Burroughs  Is a corresponding author
  1. University of Warwick, United Kingdom

Abstract

Chromosome segregation is a mechanical process that requires assembly of the mitotic spindle - a dynamic microtubule-based force-generating machine. Connections to this spindle are mediated by sister kinetochore pairs, that form dynamic end-on attachments to microtubules emanating from opposite spindle poles. This bi-orientation generates forces that have been reported to stretch the kinetochore itself, which has been suggested to silence the spindle checkpoint and allow anaphase onset. We reveal using three dimensional tracking that the outer kinetochore domain can swivel around the inner kinetochore/centromere, which results in large reductions in intra-kinetochore distance (delta) when viewed in lower dimensions. We show that swivel provides a mechanical flexibility that enables kinetochores at the periphery of the spindle to engage microtubules. Swivel rather than delta reduces as cells approach anaphase, suggesting an organisational change linked to checkpoint satisfaction and/or obligatory changes in kinetochore mechanochemistry may occur before dissolution of sister chromatid cohesion.

Article and author information

Author details

  1. Chris A Smith

    Centre for Mechanochemical Cell Biology, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Andrew D McAinsh

    Centre for Mechanochemical Cell Biology, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom
    For correspondence
    A.D.McAinsh@warwick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6808-0711
  3. Nigel J Burroughs

    Warwick Systems Biology Centre, Mathematics Institute, University of Warwick, Coventry, United Kingdom
    For correspondence
    N.J.Burroughs@warwick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Funding

Engineering and Physical Sciences Research Council (EP/F500378/1)

  • Chris A Smith

Wellcome (106151/Z/14/Z)

  • Andrew D McAinsh

Biotechnology and Biological Sciences Research Council (BB/I021353/1)

  • Andrew D McAinsh
  • Nigel J Burroughs

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

Reviewing Editor

  1. Andrea Musacchio, Max Planck Institute of Molecular Physiology, Germany

Publication history

  1. Received: March 18, 2016
  2. Accepted: September 2, 2016
  3. Accepted Manuscript published: September 3, 2016 (version 1)
  4. Version of Record published: October 4, 2016 (version 2)

Copyright

© 2016, Smith 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. Chris A Smith
  2. Andrew D McAinsh
  3. Nigel J Burroughs
(2016)
Human kinetochores are swivel joints that mediate microtubule attachments
eLife 5:e16159.
https://doi.org/10.7554/eLife.16159
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