The binding of Borealin to microtubules underlies a tension independent kinetochore-microtubule error correction pathway

Prasad Trivedi, Anatoly V. Zaytsev, Maxim Godzi, Fazly I. Ataullakhanov, Ekaterina L. Grishchuk () and P. Todd Stukenberg ()
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Prasad Trivedi: University of Virginia
Anatoly V. Zaytsev: University of Pennsylvania
Maxim Godzi: Russian Academy of Sciences
Fazly I. Ataullakhanov: Russian Academy of Sciences
Ekaterina L. Grishchuk: University of Pennsylvania
P. Todd Stukenberg: University of Virginia

Nature Communications, 2019, vol. 10, issue 1, 1-19

Abstract: Abstract Proper chromosome segregation depends upon kinetochore phosphorylation by the Chromosome Passenger Complex (CPC). Current models suggest the activity of the CPC decreases in response to the inter-kinetochore stretch that accompanies the formation of bi-oriented microtubule attachments, however little is known about tension-independent CPC phosphoregulation. Microtubule bundles initially lie in close proximity to inner centromeres and become depleted by metaphase. Here we find these microtubules control kinetochore phosphorylation by the CPC in a tension independent manner via a microtubule-binding site on the Borealin subunit. Disruption of Borealin-microtubule interactions generates reduced phosphorylation of prometaphase kinetochores, improper kinetochore-microtubule attachments and weakened spindle checkpoint signals. Experimental and modeling evidence suggests that kinetochore phosphorylation is greatly stimulated when the CPC binds microtubules that lie near the inner centromere, even if kinetochores have high inter-kinetochore stretch. We propose the CPC senses its local environment through microtubule structures to control phosphorylation of kinetochores.

Date: 2019
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DOI: 10.1038/s41467-019-08418-4

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