Adaptive changes in the kinetochore architecture facilitate proper spindle assembly

Valentin Magidson, Raja Paul, Nachen Yang, Jeffrey G. Ault, Christopher B. O'Connell, Irina Tikhonenko, Bruce F. Mcewen, Alex Mogilner, Alexey Khodjakov

Research output: Contribution to journalArticle

Abstract

Mitotic spindle formation relies on the stochastic capture of microtubules at kinetochores. Kinetochore architecture affects the efficiency and fidelity of this process with large kinetochores expected to accelerate assembly at the expense of accuracy, and smaller kinetochores to suppress errors at the expense of efficiency. We demonstrate that on mitotic entry, kinetochores in cultured human cells form large crescents that subsequently compact into discrete structures on opposite sides of the centromere. This compaction occurs only after the formation of end-on microtubule attachments. Live-cell microscopy reveals that centromere rotation mediated by lateral kinetochore-microtubule interactions precedes the formation of end-on attachments and kinetochore compaction. Computational analyses of kinetochore expansion-compaction in the context of lateral interactions correctly predict experimentally observed spindle assembly times with reasonable error rates. The computational model suggests that larger kinetochores reduce both errors and assembly times, which can explain the robustness of spindle assembly and the functional significance of enlarged kinetochores.

Original languageEnglish (US)
Pages (from-to)1134-1144
Number of pages11
JournalNature Cell Biology
Volume17
Issue number9
DOIs
StatePublished - Sep 1 2015

ASJC Scopus subject areas

  • Cell Biology

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    Magidson, V., Paul, R., Yang, N., Ault, J. G., O'Connell, C. B., Tikhonenko, I., Mcewen, B. F., Mogilner, A., & Khodjakov, A. (2015). Adaptive changes in the kinetochore architecture facilitate proper spindle assembly. Nature Cell Biology, 17(9), 1134-1144. https://doi.org/10.1038/ncb3223