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NDC80 clustering modulates microtubule dynamics under force

View ORCID ProfileVladimir A. Volkov, View ORCID ProfilePim J. Huis in't Veld, Marileen Dogterom, View ORCID ProfileAndrea Musacchio
doi: https://doi.org/10.1101/198291
Vladimir A. Volkov
1Department of Bionanoscience, Faculty of Applied Sciences, Delft University of Technology, van der Maasweg 9, 2629HZ Delft, the Netherlands
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Pim J. Huis in't Veld
2Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany
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Marileen Dogterom
1Department of Bionanoscience, Faculty of Applied Sciences, Delft University of Technology, van der Maasweg 9, 2629HZ Delft, the Netherlands
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  • For correspondence: m.dogterom@tudelft.nl andrea.musacchio@mpi-dortmund.mpg.de
Andrea Musacchio
2Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany
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  • For correspondence: m.dogterom@tudelft.nl andrea.musacchio@mpi-dortmund.mpg.de
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Abstract

Multivalency, the presence of multiple interfaces for intermolecular interactions, underlies many biological phenomena, including receptor clustering and cytosolic condensation. One of its ultimate purposes is to increase binding affinity, but systematic analyses of its role in complex biological assemblies have been rare. Presence of multiple copies of the microtubule-binding NDC80 complex is an evolutionary conserved but poorly characterized feature of kinetochores, the points of attachment of chromosomes to spindle microtubules. To address its significance, we engineered modules allowing incremental addition of NDC80 complexes. The modules’ residence time on microtubules increased exponentially with the number of NDC80 complexes. While modules containing a single NDC80 complex were unable to track depolymerizing microtubules, modules with two or more complexes tracked depolymerizing microtubules and stiffened the connection with microtubules under force. Cargo-conjugated modules of divalent or trivalent NDC80 stalled and rescued microtubule depolymerization in a force-dependent manner. Thus, multivalent microtubule binding through NDC80 clustering is crucial for force-induced modulation of kinetochore-microtubule attachments.

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Posted October 04, 2017.
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NDC80 clustering modulates microtubule dynamics under force
Vladimir A. Volkov, Pim J. Huis in't Veld, Marileen Dogterom, Andrea Musacchio
bioRxiv 198291; doi: https://doi.org/10.1101/198291
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NDC80 clustering modulates microtubule dynamics under force
Vladimir A. Volkov, Pim J. Huis in't Veld, Marileen Dogterom, Andrea Musacchio
bioRxiv 198291; doi: https://doi.org/10.1101/198291

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