Tension promotes kinetochore-microtubule release by Aurora B kinase

To ensure accurate chromosome segregation, interactions between kinetochores and microtubules are regulated by a combination of mechanics and biochemistry. Tension provides a signal to discriminate attachment errors from bi-oriented kinetochores with sisters correctly attached to opposite spindle po...

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Veröffentlicht in:The Journal of cell biology 2021-06, Vol.220 (6), p.1
Hauptverfasser: Chen, Geng-Yuan, Renda, Fioranna, Zhang, Huaiying, Gokden, Alper, Wu, Daniel Z, Chenoweth, David M, Khodjakov, Alexey, Lampson, Michael A
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Sprache:eng
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Zusammenfassung:To ensure accurate chromosome segregation, interactions between kinetochores and microtubules are regulated by a combination of mechanics and biochemistry. Tension provides a signal to discriminate attachment errors from bi-oriented kinetochores with sisters correctly attached to opposite spindle poles. Biochemically, Aurora B kinase phosphorylates kinetochores to destabilize interactions with microtubules. To link mechanics and biochemistry, current models regard tension as an input signal to locally regulate Aurora B activity. Here, we show that the outcome of kinetochore phosphorylation depends on tension. Using optogenetics to manipulate Aurora B at individual kinetochores, we find that kinase activity promotes microtubule release when tension is high. Conversely, when tension is low, Aurora B activity promotes depolymerization of kinetochore-microtubules while maintaining attachment. Thus, phosphorylation converts a catch-bond, in which tension stabilizes attachments, to a slip-bond, which releases microtubules under tension. We propose that tension is a signal inducing distinct error-correction pathways, with release or depolymerization being advantageous for typical errors characterized by high or low tension, respectively.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.202007030