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

eLife (2020-12-22)
Peter Jan Hooikaas, Hugo Gj Damstra, Oane J Gros, Wilhelmina E van Riel, Maud Martin, Yesper Th Smits, Jorg van Loosdregt, Lukas C Kapitein, Florian Berger, Anna Akhmanova
RESUMO

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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Sigma-Aldrich
Phorbol 12-myristate 13-acetate, ≥99% (TLC), film or powder
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Ionomycin calcium salt from Streptomyces conglobatus, powder, ≥98% (HPLC)
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Sodium acrylate, 97%
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Anti-α-Tubulin antibody, Mouse monoclonal, clone DM1A, purified from hybridoma cell culture
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Vinblastine sulfate salt, ≥97% (HPLC)
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Anti-CEP135 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-KIF21B antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution