Multivalency of NDC80 in the outer kinetochore is essential to track shortening microtubules and generate forces

Multivalency of NDC80 in the outer kinetochore is essential to track shortening microtubules and generate forces

Volkov, V. (TU Delft BN/Marileen Dogterom Lab)
Huis In ’T Veld, Pim J. (Max Planck Institute of Molecular Physiology)
Dogterom, A.M. (TU Delft BN/Bionanoscience)
Musacchio, Andrea (Max Planck Institute of Molecular Physiology)

BN/Bionanoscience

2018

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 attachments to 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.

http://resolver.tudelft.nl/uuid:a320d956-fc11-4de2-b64f-7e5e1ad7fecc

https://doi.org/10.7554/eLife.36764

2050-084X

eLife, 7

Institutional Repository

journal article

© 2018 V. Volkov, Pim J. Huis In ’T Veld, A.M. Dogterom, Andrea Musacchio