A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging

EMBO J. 2011 Mar 2;30(5):906-19. doi: 10.1038/emboj.2011.15. Epub 2011 Feb 4.


Kinetochore fibres (K-fibres) of the spindle apparatus move chromosomes during mitosis. These fibres are discrete bundles of parallel microtubules (MTs) that are crosslinked by inter-MT 'bridges' that are thought to improve fibre stability during chromosomal movement. The identity of these bridges is unknown. Clathrin is a multimeric protein that has been shown to stabilise K-fibres during early mitosis by a mechanism independent of its role in membrane trafficking. In this study, we show that clathrin at the mitotic spindle is in a transforming acidic colied-coil protein 3 (TACC3)/colonic, hepatic tumour overexpressed gene (ch-TOG)/clathrin complex. The complex is anchored to the spindle by TACC3 and ch-TOG. Ultrastructural analysis of clathrin-depleted K-fibres revealed a selective loss of a population of short inter-MT bridges and a general loss of MTs. A similar loss of short inter-MT bridges was observed in TACC3-depleted K-fibres. Finally, immunogold labelling confirmed that inter-MT bridges in K-fibres contain clathrin. Our results suggest that the TACC3/ch-TOG/clathrin complex is an inter-MT bridge that stabilises K-fibres by physical crosslinking and by reducing rates of MT catastrophe.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinases
  • Clathrin / genetics
  • Clathrin / metabolism*
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Kinetochores / physiology*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / genetics
  • Microtubules / metabolism*
  • Mitosis
  • Phosphorylation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Transport
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism*


  • CKAP5 protein, human
  • Clathrin
  • Microtubule-Associated Proteins
  • RNA, Messenger
  • TACC3 protein, human
  • Aurora Kinases
  • Protein Serine-Threonine Kinases