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Nek2 activation of Kif24 ensures cilium disassembly during the cell cycle

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  • Sehyun Kim

    (New York University Cancer Institute, New York University School of Medicine
    Present address: Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA)

  • Kwanwoo Lee

    (New York University Cancer Institute, New York University School of Medicine)

  • Jung-Hwan Choi

    (Skirball Institute of Biomolecular Medicine, Molecular Neurobiology Program, New York University School of Medicine
    New York University School of Medicine)

  • Niels Ringstad

    (Skirball Institute of Biomolecular Medicine, Molecular Neurobiology Program, New York University School of Medicine
    New York University School of Medicine)

  • Brian David Dynlacht

    (New York University Cancer Institute, New York University School of Medicine)

Abstract

Many proteins are known to promote ciliogenesis, but mechanisms that promote primary cilia disassembly before mitosis are largely unknown. Here we identify a mechanism that favours cilium disassembly and maintains the disassembled state. We show that co-localization of the S/G2 phase kinase, Nek2 and Kif24 triggers Kif24 phosphorylation, inhibiting cilia formation. We show that Kif24, a microtubule depolymerizing kinesin, is phosphorylated by Nek2, which stimulates its activity and prevents the outgrowth of cilia in proliferating cells, independent of Aurora A and HDAC6. Our data also suggest that cilium assembly and disassembly are in dynamic equilibrium, but Nek2 and Kif24 can shift the balance toward disassembly. Further, Nek2 and Kif24 are overexpressed in breast cancer cells, and ablation of these proteins restores ciliation in these cells, thereby reducing proliferation. Thus, Kif24 is a physiological substrate of Nek2, which regulates cilia disassembly through a concerted mechanism involving Kif24-mediated microtubule depolymerization.

Suggested Citation

  • Sehyun Kim & Kwanwoo Lee & Jung-Hwan Choi & Niels Ringstad & Brian David Dynlacht, 2015. "Nek2 activation of Kif24 ensures cilium disassembly during the cell cycle," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9087
    DOI: 10.1038/ncomms9087
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    Cited by:

    1. Sarah E. Conduit & Wayne Pearce & Amandeep Bhamra & Benoit Bilanges & Laura Bozal-Basterra & Lazaros C. Foukas & Mathias Cobbaut & Sandra D. Castillo & Mohammad Amin Danesh & Mahreen Adil & Arkaitz Ca, 2024. "A class I PI3K signalling network regulates primary cilia disassembly in normal physiology and disease," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Muqing Cao & Xiaoxiao Zou & Chaoyi Li & Zaisheng Lin & Ni Wang & Zhongju Zou & Youqiong Ye & Joachim Seemann & Beth Levine & Zaiming Tang & Qing Zhong, 2023. "An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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