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Nek5 promotes centrosome integrity in interphase and loss of centrosome cohesion in mitosis

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journal contribution
posted on 26.05.2015, 11:10 by Suzanna L. Prosser, Navdeep K. Sahota, L. Pelletier, C. G. Morrison, Andrew M. Fry
Nek5 is a poorly characterized member of the NIMA-related kinase family, other members of which play roles in cell cycle progression and primary cilia function. Here, we show that Nek5, similar to Nek2, localizes to the proximal ends of centrioles. Depletion of Nek5 or overexpression of kinase-inactive Nek5 caused unscheduled separation of centrosomes in interphase, a phenotype also observed upon overexpression of active Nek2. However, separated centrosomes that resulted from Nek5 depletion remained relatively close together, exhibited excess recruitment of the centrosome linker protein rootletin, and had reduced levels of Nek2. In addition, Nek5 depletion led to loss of PCM components, including γ-tubulin, pericentrin, and Cdk5Rap2, with centrosomes exhibiting reduced microtubule nucleation. Upon mitotic entry, Nek5-depleted cells inappropriately retained centrosome linker components and exhibited delayed centrosome separation and defective chromosome segregation. Hence, Nek5 is required for the loss of centrosome linker proteins and enhanced microtubule nucleation that lead to timely centrosome separation and bipolar spindle formation in mitosis.

Funding

This work was supported by the Wellcome Trust (082828; to A.M. Fry), the Biotechnology and Biological Sciences Research Council (A.M. Fry), a Science Foundation Ireland Principal Investigator award 10/IN.1/B2972 (to C.G. Morrison), Canadian Institutes of Health Research (MOP-123468; to L. Pelletier), and the Krembil Foundation (to L. Pelletier).

History

Citation

Journal of Cell Biology, 2015, 209 (3), pp. 339-348 (10)

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Biochemistry

Version

VoR (Version of Record)

Published in

Journal of Cell Biology

Publisher

Rockefeller University Press

issn

0021-9525

eissn

1540-8140

Available date

26/05/2015

Publisher version

http://jcb.rupress.org/content/209/3/339

Notes

Supplemental Material can be found at http://jcb.rupress.org/content/suppl/2015/05/08/jcb.201412099.DC1.html

Language

en

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