Astrin-SKAP complex reconstitution reveals its kinetochore interaction with microtubule-bound Ndc80
- Whitehead Institute, United States
- The Scripps Research Institute, United States
Abstract
Chromosome segregation requires robust interactions between the macromolecular kinetochore structure and dynamic microtubule polymers. A key outstanding question is how kinetochore-microtubule attachments are modulated to ensure that bi-oriented attachments are selectively stabilized and maintained. The Astrin-SKAP complex localizes preferentially to properly bi-oriented sister kinetochores, representing the final outer kinetochore component recruited prior to anaphase onset. Here, we reconstitute the 4-subunit Astrin-SKAP complex, including a novel MYCBP subunit. Our work demonstrates that the Astrin-SKAP complex contains separable kinetochore localization and microtubule binding domains. In addition, through cross-linking analysis in human cells and biochemical reconstitution, we show that the Astrin-SKAP complex binds synergistically to microtubules with the Ndc80 complex to form an integrated interface. We propose a model in which the Astrin-SKAP complex acts together with the Ndc80 complex to stabilize correctly formed kinetochore-microtubule interactions.
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Funding
National Institute of General Medical Sciences (GM088313)
- Iain M Cheeseman
Leukemia and Lymphoma Society (Scholar Award)
- Iain M Cheeseman
National Institute of General Medical Sciences (GM052468)
- Elizabeth M Wilson-Kubalek
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Kern et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Astrin-SKAP complex reconstitution reveals its kinetochore interaction with microtubule-bound Ndc80
eLife 6:e26866.
https://doi.org/10.7554/eLife.26866
