Molecular determinants of the Ska-Ndc80 interaction and their influence on microtubule tracking and force-coupling
- Max Planck Institute of Molecular Physiology, Germany
- Delft University of Technology, Netherlands
Abstract
Errorless chromosome segregation requires load-bearing attachments of the plus ends of spindle microtubules to chromosome structures named kinetochores. How these end-on kinetochore attachments are established following initial lateral contacts with the microtubule lattice is poorly understood. Two microtubule-binding complexes, the Ndc80 and Ska complexes, are important for efficient end-on coupling and may function as a unit in this process, but precise conditions for their interaction are unknown. Here, we report that the Ska-Ndc80 interaction is phosphorylation-dependent and does not require microtubules, applied force, or several previously identified functional determinants including the Ndc80-loop and the Ndc80-tail. Both the Ndc80-tail, which we reveal to be essential for microtubule end-tracking, and Ndc80-bound Ska stabilize microtubule ends in a stalled conformation. Modulation of force-coupling efficiency demonstrates that the duration of stalled microtubule disassembly predicts whether a microtubule is stabilized and rescued by the kinetochore, likely reflecting a structural transition of the microtubule end.
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All relevant data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Pim J Huis in 't Veld
Funding
European Commission (ERC AdG RECEPIANCE (proposal 669686))
- Andrea Musacchio
Deutsche Forschungsgemeinschaft (CRC1093)
- Andrea Musacchio
European Commission (ERC SG MODELCELL (proposal 609822))
- Marileen Dogterom
European Molecular Biology Organization (STF7203)
- Pim J Huis in 't Veld
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Huis in 't Veld 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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Molecular determinants of the Ska-Ndc80 interaction and their influence on microtubule tracking and force-coupling
eLife 8:e49539.
https://doi.org/10.7554/eLife.49539
