Molecular determinants of the Ska-Ndc80 interaction and their influence on microtubule tracking and force-coupling
Pim J. Huis In 't Veld (Max Planck Institute of Molecular Physiology)
Vladimir A. Volkov (TU Delft - Applied Sciences)
Isabelle D. Stender (Max Planck Institute of Molecular Physiology)
Andrea Musacchio (Universität Duisburg-Essen, Max Planck Institute of Molecular Physiology)
Marileen Dogterom (TU Delft - Applied Sciences)
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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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