Tension promotes kinetochore-microtubule release by Aurora B kinase
| Autor: | Alexey Khodjakov, Huaiying Zhang, David M. Chenoweth, Michael A. Lampson, Geng-Yuan Chen, Fioranna Renda, Daniel Z Wu, Alper Gokden |
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| Rok vydání: | 2020 |
| Předmět: |
Technology
Aurora B kinase Mitosis Biology Microtubules Spindle pole body Kinetochore microtubule Chromosome segregation 03 medical and health sciences 0302 clinical medicine Microtubule Chromosome Segregation Tensins Report Aurora Kinase B Humans Kinase activity Phosphorylation Kinetochores 030304 developmental biology 0303 health sciences Kinetochore Cell Biology Biophysics 030217 neurology & neurosurgery HeLa Cells Cell Cycle and Division |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 |
| Popis: | Chen et al. show how kinetochores integrate mechanics and biochemistry using optogenetic manipulation of Aurora B kinase. Aurora B promotes microtubule depolymerization at low tension or microtubule release at high tension. Thus, tension is a signal inducing distinct error-correction pathways. 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. |
| Databáze: | OpenAIRE |
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