Stable kinetochore-microtubule attachment requires loop-dependent Ndc80-Ndc80 binding
Soumitra Polley (Max Planck Institute of Molecular Physiology)
Helen Müschenborn (Max Planck Institute of Molecular Physiology)
Melina Terbeck (Max Planck Institute of Molecular Physiology)
Anna De Antoni (European Institute of Oncology IRCCS)
Ingrid R. Vetter (Max Planck Institute of Molecular Physiology)
Marileen Dogterom (TU Delft - BN/Marileen Dogterom Lab)
Andrea Musacchio (Universität Duisburg-Essen, Max Planck Institute of Molecular Physiology)
Vladimir A. Volkov (TU Delft - BN/Marileen Dogterom Lab, Queen Mary University of London)
Pim J. Huis in 't Veld (Max Planck Institute of Molecular Physiology)
More Info
expand_more
Other than for strictly personal use, it is not permitted to download, forward or distribute the text or part of it, without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license such as Creative Commons.
Abstract
During cell division, kinetochores link chromosomes to spindle microtubules. The Ndc80 complex, a crucial microtubule binder, populates each kinetochore with dozens of copies. Whether adjacent Ndc80 complexes cooperate to promote microtubule binding remains unclear. Here we demonstrate that the Ndc80 loop, a short sequence that interrupts the Ndc80 coiled-coil at a conserved position, folds into a more rigid structure than previously assumed and promotes direct interactions between full-length Ndc80 complexes on microtubules. Mutations in the loop impair these Ndc80-Ndc80 interactions, prevent the formation of force-resistant kinetochore-microtubule attachments, and cause cells to arrest in mitosis for hours. This arrest is not due to an inability to recruit the kinetochore-microtubule stabilizing SKA complex and cannot be overridden by mutations in the Ndc80 tail that strengthen microtubule attachment. Thus, loop-mediated organization of adjacent Ndc80 complexes is crucial for stable end-on kinetochore-microtubule attachment and spindle assembly checkpoint satisfaction.
help_outline