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Published online
doi:10.1083/jcb.200809055
The Journal of Cell Biology, Vol. 184, No. 3, 365-372
The Rockefeller University Press, 0021-9525 $30.00
© Toso et al.
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Kinetochore-generated pushing forces separate centrosomes during bipolar spindle assembly



Alberto Toso1, Jennifer R. Winter2, Ainslie J. Garrod2, Ana C. Amaro1, Patrick Meraldi1, and Andrew D. McAinsh2

1 Institute of Biochemistry, ETH Zurich, CH-8093 Zurich, Switzerland
2 Chromosome Segregation Laboratory, Marie Curie Research Institute, Oxted, Surrey RH8 0TL, England, UK

Correspondence to Patrick Meraldi: patrick.meraldi{at}bc.biol.ethz.ch; or Andrew D. McAinsh: a.mcainsh{at}mcri.ac.uk

In animal somatic cells, bipolar spindle formation requires separation of the centrosome-based spindle poles. Centrosome separation relies on multiple pathways, including cortical forces and antiparallel microtubule (MT) sliding, which are two activities controlled by the protein kinase aurora A. We previously found that depletion of the human kinetochore protein Mcm21RCENP-O results in monopolar spindles, raising the question as to whether kinetochores contribute to centrosome separation. In this study, we demonstrate that kinetochores promote centrosome separation after nuclear envelope breakdown by exerting a pushing force on the kinetochore fibers (k-fibers), which are bundles of MTs that connect kinetochores to centrosomes. This force is based on poleward MT flux, which incorporates new tubulin subunits at the plus ends of k-fibers and requires stable k-fibers to drive centrosomes apart. This kinetochore-dependent force becomes essential for centrosome separation if aurora A is inhibited. We conclude that two mechanisms control centrosome separation during prometaphase: an aurora A–dependent pathway and a kinetochore-dependent pathway that relies on k-fiber–generated pushing forces.

A. Toso and J.R. Winter contributed equally to this paper.

Abbreviations used in this paper: CENP-E, centromere protein E; hTERT, human telomerase reverse transcriptase; k-fiber, kinetochore fiber; MCAK, mitotic centromere-associated kinesin; mRFP, monomeric RFP; MT, microtubule; NEBD, nuclear envelope breakdown; PA, photoactivatable.

© 2009 Toso et al.
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