Nek9 phosphorylation defines a new role for TPX2 in Eg5-dependent centrosome separation before nuclear envelope breakdown

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  • dc.contributor.author Eibes, Susana
  • dc.contributor.author Gallisà-Suñé, Núria
  • dc.contributor.author Rosas Salvans, Miquel, 1987-
  • dc.contributor.author Martínez-Delgado, Paula
  • dc.contributor.author Vernos, Isabelle, 1959-
  • dc.contributor.author Roig, Joan
  • dc.date.available 2019-11-07T07:33:31Z
  • dc.date.issued 2018
  • dc.description.abstract Centrosomes [1, 2] play a central role during spindle assembly in most animal cells [3]. In early mitosis, they organize two symmetrical microtubule arrays that upon separation define the two poles of the forming spindle. Centrosome separation is tightly regulated [4, 5], occurring through partially redundant mechanisms that rely on the action of microtubule-based dynein and kinesin motors and the actomyosin system [6]. While centrosomes can separate in prophase or in prometaphase after nuclear envelope breakdown (NEBD), prophase centrosome separation optimizes spindle assembly and minimizes the occurrence of abnormal chromosome attachments that could end in aneuploidy [7, 8]. Prophase centrosome separation relies on the activity of Eg5/KIF11, a mitotic kinesin [9] that accumulates around centrosomes in early mitosis under the control of CDK1 and the Nek9/Nek6/7 kinase module [10-17]. Here, we show that Eg5 localization and centrosome separation in prophase depend on the nuclear microtubule-associated protein TPX2 [18], a pool of which localizes to the centrosomes before NEBD. This localization involves RHAMM/HMMR [19] and the kinase Nek9 [20], which phosphorylates TPX2 nuclear localization signal (NLS) preventing its interaction with importin and nuclear import. The pool of centrosomal TPX2 in prophase has a critical role for both microtubule aster organization and Eg5 localization, and thereby for centrosome separation. Our results uncover an unsuspected role for TPX2 before NEBD and define a novel regulatory mechanism for centrosome separation in prophase. They furthermore suggest NLS phosphorylation as a novel regulatory mechanism for spindle assembly factors controlled by the importin/Ran system.
  • dc.description.sponsorship This work was funded by the Ministerio de Economía, Industria y Competitividad (MINECO) from Spain through Plan Nacional de I+D grants BFU2014-58422 (to J.R.) and BFU2012-37163 (to I.V.). N.G.-S. and M.R.-S. are recipients of FPI Fellowships BES-2015-072446 and BES-2013-064601 from MINECO. IRB Barcelona and CRG are Severo Ochoa Award of Excellence recipients from MINECO. J.R. would like to thank the IRB Barcelona for its enduring institutional support.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Eibes S, Gallisà-Suñé N, Rosas-Salvans M, Martínez-Delgado P, Vernos I, Roig J. Nek9 phosphorylation defines a new role for TPX2 in Eg5-dependent centrosome separation before nuclear envelope breakdown. Curr Biol. 2018;28(1):121-9. DOI: 10.1016/j.cub.2017.11.046
  • dc.identifier.doi http://dx.doi.org/10.1016/j.cub.2017.11.046
  • dc.identifier.issn 0960-9822
  • dc.identifier.uri http://hdl.handle.net/10230/42768
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Current Biology. 2018;28(1):121-9
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-58422
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-37163
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BES2015-072446
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BES2013-064601
  • dc.rights © Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.cub.2017.11.046 that appeared in the journal Current Biology. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: https://www.elsevier.com/about/our-business/policies/open-access-licenses/elsevier-user-license
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://www.elsevier.com/open-access/userlicense/1.0/
  • dc.subject.keyword Prophase
  • dc.subject.keyword Centrosome separation
  • dc.subject.keyword Eg5
  • dc.subject.keyword TPX2
  • dc.subject.keyword NIMA kinases
  • dc.subject.keyword Nek9
  • dc.title Nek9 phosphorylation defines a new role for TPX2 in Eg5-dependent centrosome separation before nuclear envelope breakdown
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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