2. Academic Validation
  3. TD-60 links RalA GTPase function to the CPC in mitosis

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

  • Nat Commun. 2015 Jul 9;6:7678. doi: 10.1038/ncomms8678.
Diana Papini 1,  Lars Langemeyer 2,  Maria A Abad 3,  Alastair Kerr 3,  Itaru Samejima 3,  Patrick A Eyers 4,  A Arockia Jeyaprakash 3,  Jonathan M G Higgins 5,  Francis A Barr 2,  William C Earnshaw 3
Affiliations

Affiliations

  • 1 1] Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Max Born Crescent, Edinburgh EH9 3BF, UK [2] Institute for Cell and Molecular Biosciences (ICaMB), Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • 2 Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
  • 3 Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Max Born Crescent, Edinburgh EH9 3BF, UK.
  • 4 Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Crown St, Liverpool L69 7ZB, UK.
  • 5 Institute for Cell and Molecular Biosciences (ICaMB), Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
PMID: 26158537 DOI: 10.1038/ncomms8678
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.

Figures