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Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1

Author

Listed:
  • Hitesh Patel

    (Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Judith Zich

    (Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh)

  • Bryan Serrels

    (Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Colin Rickman

    (Institute of Biological Chemistry, Biophysics and Bioengineering School of Engineering and Physical Sciences, Heriot-Watt University)

  • Kevin G. Hardwick

    (Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh)

  • Margaret C. Frame

    (Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Valerie G. Brunton

    (Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh)

Abstract

Kindlin-1 binds to integrins and regulates integrin activation at cell adhesions. Here we report a new function of Kindlin-1 in regulating spindle assembly. We show that Kindlin-1 localizes to centrosomes, its concentration peaking during G2/M, where it associates with various pericentriolar material proteins, including Polo-like kinase 1. Short interfering RNA-mediated depletion of Kindlin-1 increases formation of abnormal mitotic spindles and decreases cellular survival. This effect is dependent not only on the ability of Kindlin-1 to bind integrins but also on Polo-like kinase 1-mediated Kindlin-1 phosphorylation. We demonstrate that a subcellular pool of phosphorylated Kindlin-1 is located exclusively at centrosomes. Our work identifies a novel cellular role for Kindlin-1 in ensuring mitotic spindle assembly and cellular survival that is controlled by phosphorylation via Polo-like kinase 1.

Suggested Citation

  • Hitesh Patel & Judith Zich & Bryan Serrels & Colin Rickman & Kevin G. Hardwick & Margaret C. Frame & Valerie G. Brunton, 2013. "Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1," Nature Communications, Nature, vol. 4(1), pages 1-9, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3056
    DOI: 10.1038/ncomms3056
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