Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/45195
Title: Mitotic phosphorylation by NEK6 and NEK7 reduces microtubule affinity of EML4 to promote chromosome congression
Authors: Fry, A
Adib, R
Montgomery, J
Atherton, J
O'Regan, L
Richards, M
Straatman, K
Roth, D
Straube, A
Bayliss, R
Moores, C
First Published: 13-Aug-2019
Publisher: American Association for the Advancement of Science
Citation: Science Signaling, 2019, In Press
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.
DOI Link: TBA
ISSN: 1937-9145
Links: TBA
http://hdl.handle.net/2381/45195
Embargo on file until: 1-Jan-10000
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2019, American Association for the Advancement of Science. Deposited with reference to the publisher’s open access archiving policy. (http://www.rioxx.net/licenses/all-rights-reserved)
Description: The file associated with this record is under embargo until publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Molecular and Cell Biology

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