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Mitotic phosphorylation by NEK6 and NEK7 reduces the microtubule affinity of EML4 to promote chromosome congression
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Adib, Rozita, Montgomery, Jessica, Atherton, Joseph, O'Regan, Laura, Richards, Mark W., Straatman, Kees, Roth, Daniel, Straube, Anne, Bayliss, Richard, Moores, Carolyn and Fry, Andrew M. (2019) Mitotic phosphorylation by NEK6 and NEK7 reduces the microtubule affinity of EML4 to promote chromosome congression. Science Signalling, 12 (594). eaaw2939. doi:10.1126/scisignal.aaw2939
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WRAP-mitotic-phosphorylation-NEK6-chromosome-Straube-2019.pdf - Accepted Version - Requires a PDF viewer. Download (46Mb) | Preview |
Official URL: https://doi.org/10.1126/scisignal.aaw2939
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. In addition, constitutive activation of NEK6 or NEK7 reduced the association of EML4 with interphase microtubules. Together, these data support a model in which NEK6- and NEK7-dependent phosphorylation promotes the dissociation of EML4 from microtubules in mitosis in a manner that is required for efficient chromosome congression.
| Item Type: | Journal Article | |||||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Tubulins, Microtubules, Microtubules -- Stability, Chromosome inversions , Mitosis | |||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Science Signalling | |||||||||||||||||||||||||||||||||
| Publisher: | American Association for the Advancement of Science | |||||||||||||||||||||||||||||||||
| ISSN: | 1937-9145 | |||||||||||||||||||||||||||||||||
| Official Date: | 13 August 2019 | |||||||||||||||||||||||||||||||||
| Dates: |
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| Volume: | 12 | |||||||||||||||||||||||||||||||||
| Number: | 594 | |||||||||||||||||||||||||||||||||
| Article Number: | eaaw2939 | |||||||||||||||||||||||||||||||||
| DOI: | 10.1126/scisignal.aaw2939 | |||||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||||||||||||||
| Publisher Statement: | “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 in Science Signalling on 12(594), eaaw2939. 13/08/2019. https://doi.org/10.1126/scisignal.aaw2939 | |||||||||||||||||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||||||||||||||||||||
| Copyright Holders: | © 2019 The Authors | |||||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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