1. Cancer Biology
  2. Cell Biology

Augmin prevents merotelic attachments by promoting proper arrangement of bridging and kinetochore fibers

  1. Valentina Štimac
  2. Isabella Koprivec
  3. Martina Manenica
  4. Juraj Simunić
  5. Iva M Tolić  Is a corresponding author
  1. Ruđer Bošković Institute, Croatia
https://doi.org/10.7554/eLife.83287
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  1. Valentina Štimac
  2. Isabella Koprivec
  3. Martina Manenica
  4. Juraj Simunić
  5. Iva M Tolić
(2022)
Augmin prevents merotelic attachments by promoting proper arrangement of bridging and kinetochore fibers
eLife 11:e83287.
https://doi.org/10.7554/eLife.83287
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Abstract

The human mitotic spindle is made of microtubules nucleated at centrosomes, at kinetochores, and from pre-existing microtubules by the augmin complex. However, it is unknown how the augmin-mediated nucleation affects distinct microtubule classes and thereby mitotic fidelity. Here we use superresolution microscopy to analyze the previously indistinguishable microtubule arrangements within the crowded metaphase plate area and demonstrate that augmin is vital for the formation of uniformly arranged parallel units consisting of sister kinetochore fibers connected by a bridging fiber. This ordered geometry helps both prevent and resolve merotelic attachments. Whereas augmin-nucleated bridging fibers prevent merotelic attachments by creating a nearly parallel and highly bundled microtubule arrangement unfavorable for creating additional attachments, augmin-nucleated k-fibers produce robust force required to resolve errors during anaphase. STED microscopy revealed that bridging fibers were impaired twice as much as k-fibers following augmin depletion. The complete absence of bridging fibers from a significant portion of kinetochore pairs, especially in the inner part of the spindle, resulted in the specific reduction of the interkinetochore distance. Taken together, we propose a model where augmin promotes mitotic fidelity by generating assemblies consisting of bridging and kinetochore fibers that align sister kinetochores to face opposite poles, thereby preventing erroneous attachments.

Data availability

All source codes and source data have been deposited to the Dryad repository (https://doi.org/10.5061/dryad.fn2z34tz7).

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Author details

  1. Valentina Štimac

    Ruđer Bošković Institute, Zagreb, Croatia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0398-5493

  2. Isabella Koprivec

    Ruđer Bošković Institute, Zagreb, Croatia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6486-8261

  3. Martina Manenica

    Ruđer Bošković Institute, Zagreb, Croatia
    Competing interests
    The authors declare that no competing interests exist.

  4. Juraj Simunić

    Ruđer Bošković Institute, Zagreb, Croatia
    Competing interests
    The authors declare that no competing interests exist.

  5. Iva M Tolić

    Ruđer Bošković Institute, Zagreb, Croatia
    For correspondence
    tolic@irb.hr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1305-7922

Funding

European Research Council (ERC Consolidator Grant 647077)

  • Iva M Tolić

Croatian Science Foundation Cooperation Programme (HRZZ project PZS-2019-02-7653)

  • Iva M Tolić

European Regional Development Fund (QuantiXLie Centre of Excellence (KK.01.1.1.01.0004))

  • Iva M Tolić

European Research Council (ERC Synergy Grant 855158)

  • Iva M Tolić

European Regional Development Fund (IPSted (KK.01.1.1.04.0057))

  • Iva M Tolić

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

Reviewing Editor

  1. Thomas Surrey, Centre for Genomic Regulation (CRG), Spain

Version history

  1. Preprint posted: September 10, 2020 (view preprint)
  2. Received: September 7, 2022
  3. Accepted: September 26, 2022
  4. Accepted Manuscript published: October 21, 2022 (version 1)
  5. Version of Record published: November 7, 2022 (version 2)

Copyright

© 2022, Štimac 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. Valentina Štimac
  2. Isabella Koprivec
  3. Martina Manenica
  4. Juraj Simunić
  5. Iva M Tolić
(2022)
Augmin prevents merotelic attachments by promoting proper arrangement of bridging and kinetochore fibers
eLife 11:e83287.
https://doi.org/10.7554/eLife.83287

Share this article

https://doi.org/10.7554/eLife.83287

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