Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 4619K) PDF+supp data (9022K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Toso, A. Articles by McAinsh, A. D. Search for Related Content PubMed PubMed Citation Articles by Toso, A. Articles by McAinsh, A. D. Social Bookmarking                            What's this?

Kinetochore-generated pushing forces separate centrosomes during bipolar spindle assembly

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 Mcm21R^CENP-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.

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.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

This article has been cited by other articles:

• Dai, J., Kateneva, A. V., Higgins, J. M. G. (2009). Studies of haspin-depleted cells reveal that spindle-pole integrity in mitosis requires chromosome cohesion. J. Cell Sci. 122: 4168-4176 [Abstract] [Full Text]  
• Silk, A. D., Holland, A. J., Cleveland, D. W. (2009). Requirements for NuMA in maintenance and establishment of mammalian spindle poles. JCB 184: 677-690 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents