Kinetochore alignment within the metaphase plate is regulated by centromere stiffness and microtubule depolymerases

Khuloud Jaqaman, Emma M. King, Ana C. Amaro, Jennifer R. Winter, Jonas F. Dorn, Hunter L. Elliott, Nunu Mchedlishvili, Sarah E. McClelland, Iain M. Porter, Markus Posch, Alberto Toso, Gaudenz Danuser, Andrew D. McAinsh, Patrick Meraldi, Jason R. Swedlow

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

During mitosis in most eukaryotic cells, chromosomes align and form a metaphase plate halfway between the spindle poles, about which they exhibit oscillatory movement. These movements are accompanied by changes in the distance between sister kinetochores, commonly referred to as breathing. We developed a live cell imaging assay combined with computational image analysis to quantify the properties and dynamics of sister kinetochores in three dimensions. We show that baseline oscillation and breathing speeds in late prometaphase and metaphase are set by microtubule depolymerases, whereas oscillation and breathing periods depend on the stiffness of the mechanical linkage between sisters. Metaphase plates become thinner as cells progress toward anaphase as a result of reduced oscillation speed at a relatively constant oscillation period. The progressive slowdown of oscillation speed and its coupling to plate thickness depend nonlinearly on the stiffness of the mechanical linkage between sisters. We propose that metaphase plate formation and thinning require tight control of the state of the mechanical linkage between sisters mediated by centromeric chromatin and cohesion.

Original languageEnglish (US)
Pages (from-to)665-679
Number of pages15
JournalJournal of Cell Biology
Volume188
Issue number5
DOIs
StatePublished - Mar 8 2010

ASJC Scopus subject areas

  • Cell Biology

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    Jaqaman, K., King, E. M., Amaro, A. C., Winter, J. R., Dorn, J. F., Elliott, H. L., Mchedlishvili, N., McClelland, S. E., Porter, I. M., Posch, M., Toso, A., Danuser, G., McAinsh, A. D., Meraldi, P., & Swedlow, J. R. (2010). Kinetochore alignment within the metaphase plate is regulated by centromere stiffness and microtubule depolymerases. Journal of Cell Biology, 188(5), 665-679. https://doi.org/10.1083/jcb.200909005