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The tumour suppressor DLC2 ensures mitotic fidelity by coordinating spindle positioning and cell–cell adhesion

Author

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  • Elisa Vitiello

    (UCL Institute of Ophthalmology, University College London
    Present address: Laboratoire interdisciplinaire de Physique, Université Joseph Fourier (Grenoble 1), 38402 Saint Martin d’Hères, France)

  • Jorge G. Ferreira

    (Chromosome Instability & Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto
    Faculty of Medicine, University of Porto)

  • Helder Maiato

    (Chromosome Instability & Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto
    Faculty of Medicine, University of Porto)

  • Maria S. Balda

    (UCL Institute of Ophthalmology, University College London)

  • Karl Matter

    (UCL Institute of Ophthalmology, University College London)

Abstract

Dividing epithelial cells need to coordinate spindle positioning with shape changes to maintain cell–cell adhesion. Microtubule interactions with the cell cortex regulate mitotic spindle positioning within the plane of division. How the spindle crosstalks with the actin cytoskeleton to ensure faithful mitosis and spindle positioning is unclear. Here we demonstrate that the tumour suppressor DLC2, a negative regulator of Cdc42, and the interacting kinesin Kif1B coordinate cell junction maintenance and planar spindle positioning by regulating microtubule growth and crosstalk with the actin cytoskeleton. Loss of DLC2 induces the mislocalization of Kif1B, increased Cdc42 activity and cortical recruitment of the Cdc42 effector mDia3, a microtubule stabilizer and promoter of actin dynamics. Accordingly, DLC2 or Kif1B depletion promotes microtubule stabilization, defective spindle positioning, chromosome misalignment and aneuploidy. The tumour suppressor DLC2 and Kif1B are thus central components of a signalling network that guides spindle positioning, cell–cell adhesion and mitotic fidelity.

Suggested Citation

  • Elisa Vitiello & Jorge G. Ferreira & Helder Maiato & Maria S. Balda & Karl Matter, 2014. "The tumour suppressor DLC2 ensures mitotic fidelity by coordinating spindle positioning and cell–cell adhesion," Nature Communications, Nature, vol. 5(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6826
    DOI: 10.1038/ncomms6826
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