Multivalency of NDC80 in the outer kinetochore is essential to track shortening microtubules and generate forces
- Delft University of Technology, Netherlands
- Max Planck Institute of Molecular Physiology, Germany
Abstract
Presence of multiple copies of the microtubule-binding NDC80 complex is an evolutionary conserved feature of kinetochores, points of attachment of chromosomes to spindle microtubules. This may enable multivalent interactions with microtubules, with implications that remain unexplored. Using recombinant human kinetochore components, we show that while single NDC80 complexes do not track depolymerizing microtubules, reconstituted particles containing the NDC80 receptor CENP-T bound to three or more NDC80 complexes do so effectively, as expected for a kinetochore force coupler. To study multivalency systematically, we engineered modules allowing incremental addition of NDC80 complexes. The modules' residence time on microtubules increased exponentially with the number of NDC80 complexes. Modules with two or more complexes tracked depolymerizing microtubules with increasing efficiencies, and stalled and rescued microtubule depolymerization in a force-dependent manner when conjugated to cargo. Our observations indicate that NDC80, rather than through biased diffusion, tracks depolymerizing microtubules by harnessing force generated during microtubule disassembly.
Article and author information
Author details
Pim J Huis in 't Veld
Funding
H2020 European Research Council (669686)
- Andrea Musacchio
H2020 European Research Council (609822)
- Marileen Dogterom
European Molecular Biology Organization (7203)
- Pim J Huis in 't Veld
Deutsche Forschungsgemeinschaft (CRC1093)
- Andrea Musacchio
Max-Planck-Gesellschaft (Open-access funding)
- Andrea Musacchio
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Volkov 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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Multivalency of NDC80 in the outer kinetochore is essential to track shortening microtubules and generate forces
eLife 7:e36764.
https://doi.org/10.7554/eLife.36764
