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TD-60 links RalA GTPase function to the CPC in mitosis

Author

Listed:
  • Diana Papini

    (Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh
    Institute for Cell and Molecular Biosciences (ICaMB), Newcastle University, Medical School)

  • Lars Langemeyer

    (University of Oxford)

  • Maria A. Abad

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

  • Alastair Kerr

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

  • Itaru Samejima

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

  • Patrick A. Eyers

    (Institute of Integrative Biology, University of Liverpool)

  • A. Arockia Jeyaprakash

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

  • Jonathan M. G. Higgins

    (Institute for Cell and Molecular Biosciences (ICaMB), Newcastle University, Medical School)

  • Francis A. Barr

    (University of Oxford)

  • William C. Earnshaw

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

Abstract

TD-60 (also known as RCC2) is a highly conserved protein that structurally resembles the Ran guanine exchange factor (GEF) RCC1, but has not previously been shown to have GEF activity. TD-60 has a typical chromosomal passenger complex (CPC) distribution in mitotic cells, but associates with integrin complexes and is involved in cell motility during interphase. Here we show that TD-60 exhibits GEF activity, in vitro and in cells, for the small GTPase RalA. TD-60 or RalA depletion causes spindle abnormalities in prometaphase associated with abnormal centromeric accumulation of CPC components. TD-60 and RalA apparently work together to contribute to the regulation of kinetochore–microtubule interactions in early mitosis. Importantly, several mitotic phenotypes caused by TD-60 depletion are reverted by the expression of a GTP-locked mutant, RalA (Q72L). The demonstration that a small GTPase participates in the regulation of the CPC reveals a level of mitotic regulation not suspected in previous studies.

Suggested Citation

  • Diana Papini & Lars Langemeyer & Maria A. Abad & Alastair Kerr & Itaru Samejima & Patrick A. Eyers & A. Arockia Jeyaprakash & Jonathan M. G. Higgins & Francis A. Barr & William C. Earnshaw, 2015. "TD-60 links RalA GTPase function to the CPC in mitosis," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8678
    DOI: 10.1038/ncomms8678
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