Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells
- Utrecht University, Netherlands
- UMC Utrecht, Netherlands
Abstract
When a T cell and an antigen-presenting cell form an immunological synapse, rapid dynein-driven translocation of the centrosome towards the contact site leads to reorganization of microtubules and associated organelles. Currently, little is known about how the regulation of microtubule dynamics contributes to this process. Here, we show that the knockout of KIF21B, a kinesin-4 linked to autoimmune disorders, causes microtubule overgrowth and perturbs centrosome translocation. KIF21B restricts microtubule length by inducing microtubule pausing typically followed by catastrophe. Catastrophe induction with vinblastine prevented microtubule overgrowth and was sufficient to rescue centrosome polarization in KIF21B-knockout cells. Biophysical simulations showed that a relatively small number of KIF21B molecules can restrict microtubule length and promote an imbalance of dynein-mediated pulling forces that allows the centrosome to translocate past the nucleus. We conclude that proper control of microtubule length is important for allowing rapid remodeling of the cytoskeleton and efficient T cell polarization.
Data availability
Data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Peter Jan Hooikaas
Funding
European Research Council (609822)
- Anna Akhmanova
European Research Council (819219)
- Lukas C Kapitein
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (824.15.017)
- Anna Akhmanova
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Hooikaas 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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Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells
eLife 9:e62876.
https://doi.org/10.7554/eLife.62876
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