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Kinesin-4 kif21b limits microtubule growth to allow rapid centrosome polarization in t cells

par Hooikaas, Peter Jan;Damstra, Hugo H.G.J.;Gros, Oane O.J.;van Riel, Wilhelmina W.E.;Martin, Maud ;Smits, Yesper Y.T.H.;Loosdregt, Jorg van;Kapitein, Lukas L.C.;Berger, Florian;Akhmanova, Anna
Référence eLife, 9, page (1-75), e62876
Publication Publié, 2020-12-01

Article révisé par les pairs

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Résumé :

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.