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Molecular and Cellular Biology, July 2009, p. 3975-3990, Vol. 29, No. 14
0270-7306/09/$08.00+0     doi:10.1128/MCB.01867-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Nek6 and Nek7 Protein Kinases Are Required for Robust Mitotic Spindle Formation and Cytokinesis {triangledown} ,§

Laura O'Regan and Andrew M. Fry*

Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom

Received 8 December 2008/ Returned for modification 28 January 2009/ Accepted 27 April 2009

Nek6 and Nek7 are members of the NIMA-related serine/threonine kinase family. Previous work showed that they contribute to mitotic progression downstream of another NIMA-related kinase, Nek9, although the roles of these different kinases remain to be defined. Here, we carried out a comprehensive analysis of the regulation and function of Nek6 and Nek7 in human cells. By generating specific antibodies, we show that both Nek6 and Nek7 are activated in mitosis and that interfering with their activity by either depletion or expression of reduced-activity mutants leads to mitotic arrest and apoptosis. Interestingly, while completely inactive mutants and small interfering RNA-mediated depletion delay cells at metaphase with fragile mitotic spindles, hypomorphic mutants or RNA interference treatment combined with a spindle assembly checkpoint inhibitor delays cells at cytokinesis. Importantly, depletion of either Nek6 or Nek7 leads to defective mitotic progression, indicating that although highly similar, they are not redundant. Indeed, while both kinases localize to spindle poles, only Nek6 obviously localizes to spindle microtubules in metaphase and anaphase and to the midbody during cytokinesis. Together, these data lead us to propose that Nek6 and Nek7 play independent roles not only in robust mitotic spindle formation but also potentially in cytokinesis.

* Corresponding author. Mailing address: Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom. Phone: 44 116 229 7069. Fax: 44 116 229 7018. E-mail: amf5{at}le.ac.uk

{triangledown} Published ahead of print on 4 May 2009.

§ Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, July 2009, p. 3975-3990, Vol. 29, No. 14
0270-7306/09/$08.00+0     doi:10.1128/MCB.01867-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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