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Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells

When a T cell and an antigen-presenting cell form an immunological synapse, rapid dynein-driven translocation of the centrosome toward the contact site leads to reorganization of microtubules and associated organelles. Currently, little is known about how the regulation of microtubule dynamics contr...

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Autores principales: Hooikaas, Peter Jan, Damstra, Hugo GJ, Gros, Oane J, van Riel, Wilhelmina E, Martin, Maud, Smits, Yesper TH, van Loosdregt, Jorg, Kapitein, Lukas C, Berger, Florian, Akhmanova, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817182/
https://www.ncbi.nlm.nih.gov/pubmed/33346730
http://dx.doi.org/10.7554/eLife.62876
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author Hooikaas, Peter Jan
Damstra, Hugo GJ
Gros, Oane J
van Riel, Wilhelmina E
Martin, Maud
Smits, Yesper TH
van Loosdregt, Jorg
Kapitein, Lukas C
Berger, Florian
Akhmanova, Anna
author_facet Hooikaas, Peter Jan
Damstra, Hugo GJ
Gros, Oane J
van Riel, Wilhelmina E
Martin, Maud
Smits, Yesper TH
van Loosdregt, Jorg
Kapitein, Lukas C
Berger, Florian
Akhmanova, Anna
author_sort Hooikaas, Peter Jan
collection PubMed
description When a T cell and an antigen-presenting cell form an immunological synapse, rapid dynein-driven translocation of the centrosome toward 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 mirotubule 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.
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spelling pubmed-78171822021-01-21 Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells Hooikaas, Peter Jan Damstra, Hugo GJ Gros, Oane J van Riel, Wilhelmina E Martin, Maud Smits, Yesper TH van Loosdregt, Jorg Kapitein, Lukas C Berger, Florian Akhmanova, Anna eLife Cell Biology When a T cell and an antigen-presenting cell form an immunological synapse, rapid dynein-driven translocation of the centrosome toward 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 mirotubule 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. eLife Sciences Publications, Ltd 2020-12-21 /pmc/articles/PMC7817182/ /pubmed/33346730 http://dx.doi.org/10.7554/eLife.62876 Text en © 2020, Hooikaas et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Hooikaas, Peter Jan
Damstra, Hugo GJ
Gros, Oane J
van Riel, Wilhelmina E
Martin, Maud
Smits, Yesper TH
van Loosdregt, Jorg
Kapitein, Lukas C
Berger, Florian
Akhmanova, Anna
Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells
title Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells
title_full Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells
title_fullStr Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells
title_full_unstemmed Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells
title_short Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells
title_sort kinesin-4 kif21b limits microtubule growth to allow rapid centrosome polarization in t cells
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817182/
https://www.ncbi.nlm.nih.gov/pubmed/33346730
http://dx.doi.org/10.7554/eLife.62876
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