期刊
JOURNAL OF CELL BIOLOGY
卷 220, 期 6, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.202007030
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资金
- National Institutes of Health [GM130298, GM118510, GM122475]
- National Cancer Institute [U54-CA193417]
- Penn Center for Genome Integrity
Interactions between kinetochores and microtubules are regulated by a combination of mechanics and biochemistry, with tension and Aurora B kinase playing key roles. The outcome of kinetochore phosphorylation is tension-dependent, with high tension promoting microtubule release and low tension promoting depolymerization. This phosphorylation converts a catch-bond to a slip-bond under tension, leading to distinct error-correction pathways based on tension levels.
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.
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