BIROn - Birkbeck Institutional Research Online

    Lattice defects induced by microtubule-stabilizing agents exert a long-range effect on microtubule growth by promoting catastrophes

    Rai, A. and Liu, T. and Katrukha, E.A. and Estévez-Gallego, J. and Manka, Szymon and Paterson, I. and Díaz, F. and Kapitein, L.C. and Moores, Carolyn A. (2021) Lattice defects induced by microtubule-stabilizing agents exert a long-range effect on microtubule growth by promoting catastrophes. Proceedings of the National Academy of Sciences of the United States of America 118 (51), e2112261118. ISSN 0027-8424.

    [img] Text
    46715.pdf - Author's Accepted Manuscript
    Restricted to Repository staff only

    Download (4MB)
    46715a.pdf - Published Version of Record
    Available under License Creative Commons Attribution.

    Download (2MB) | Preview


    Microtubules are dynamic cytoskeletal polymers that spontaneously switch between phases of growth and shrinkage. The probability of transitioning from growth to shrinkage, termed catastrophe, increases with microtubule age, but the underlying mechanisms are poorly understood. Here, we set out to test whether microtubule lattice defects formed during polymerization can affect growth at the plus end. To generate microtubules with lattice defects, we used microtubule-stabilizing agents that promote formation of polymers with different protofilament numbers. By employing different agents during nucleation of stable microtubule seeds and subsequent polymerization phase, we could reproducibly induce switches in protofilament number and induce stable lattice defects. Such drug-induced defects led to frequent catastrophes, which were not observed when microtubules were grown in the same conditions but without a protofilament number mismatch. Microtubule severing at the site of the defect was sufficient to suppress catastrophes. We conclude that structural defects within microtubule lattice can exert effects that can propagate over long distances and affect the dynamic state of the microtubule end.


    Item Type: Article
    Keyword(s) / Subject(s): microtubule, catastrophe, protofilament, microtubule-stabilizing agent, Taxol
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Depositing User: Administrator
    Date Deposited: 20 Dec 2021 08:18
    Last Modified: 02 Aug 2023 18:14


    Activity Overview
    6 month trend
    6 month trend

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item