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    Mitotic phosphorylation by NEK6 and NEK7 reduces microtubule affinity of EML4 to promote chromosome congression

    Adib, R. and Montgomery, J.M. and Atherton, J. and O’Regan, L. and Richards, M.W. and Straatman, K.R. and Roth, D. and Straube, A. and Bayliss, R. and Moores, Carolyn A. and Fry, A.M. (2019) Mitotic phosphorylation by NEK6 and NEK7 reduces microtubule affinity of EML4 to promote chromosome congression. Science Signaling 12 (594), eaaw2939. ISSN 1945-0877.

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    Abstract

    EML4 is a microtubule-associated protein that promotes microtubule stability. We investigated its regulation across the cell cycle and found that EML4 was distributed as punctate foci along the microtubule lattice in interphase but exhibited reduced association with spindle microtubules in mitosis. Microtubule sedimentation and cryo-electron microscopy with 3D reconstruction revealed that the basic N-terminal domain of EML4 mediated its binding to the acidic C-terminal tails of α- and β-tubulin on the microtubule surface. The mitotic kinases NEK6 and NEK7 phosphorylated the EML4 N-terminal domain at Ser144 and Ser146 in vitro, and depletion of these kinases in cells led to increased EML4 binding to microtubules in mitosis. An S144A-S146A double mutant not only bound inappropriately to mitotic microtubules but also increased their stability and interfered with chromosome congression. Meanwhile, constitutive activation of NEK6 or NEK7 reduced EML4 association with interphase microtubules. Together, these data support a model in which NEK6- and NEK7- dependent phosphorylation promotes dissociation of EML4 from microtubules in mitosis in a manner that is required for efficient chromosome congression.

    Metadata

    Item Type: Article
    Additional Information: This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published at the link above.
    School: School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 14 Aug 2019 10:20
    Last Modified: 25 Jun 2020 14:22
    URI: https://eprints.bbk.ac.uk/id/eprint/28532

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