Augmin prevents merotelic attachments by promoting proper arrangement of bridging and kinetochore fibers
- Ruđer Bošković Institute, Croatia
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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Data from: Augmin prevents merotelic attachments by promoting proper arrangement of bridging and kinetochore fibersDryad Digital Repository, doi:10.5061/dryad.fn2z34tz7.
Article and author information
Author details
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.
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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Augmin prevents merotelic attachments by promoting proper arrangement of bridging and kinetochore fibers
eLife 11:e83287.
https://doi.org/10.7554/eLife.83287
