The Kinetochore-Bound Ska1 Complex Tracks Depolymerizing Microtubules and Binds to Curved Protofilaments

• Published in: Developmental cell 2012-11, Vol.23 (5), p.968-980
• Main Authors: Schmidt, Jens C., Arthanari, Haribabu, Boeszoermenyi, Andras, Dashkevich, Natalia M., Wilson-Kubalek, Elizabeth M., Monnier, Nilah, Markus, Michelle, Oberer, Monika, Milligan, Ron A., Bathe, Mark, Wagner, Gerhard, Grishchuk, Ekaterina L., Cheeseman, Iain M.
• Format: Article
• Language: English
• Subjects: Animals; Aurora Kinase B; Aurora Kinases; Biological and medical sciences; Caenorhabditis elegans Proteins - antagonists & inhibitors; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cell structures and functions; Chromosomal Proteins, Non-Histone - antagonists & inhibitors; Chromosomal Proteins, Non-Histone - chemistry; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosome Segregation; Cytoskeleton, cytoplasm. Intracellular movements; Fundamental and applied biological sciences. Psychology; HeLa Cells; Humans; Kinetochores - metabolism; Microtubules - metabolism; Microtubules - ultrastructure; Mitosis; Models, Molecular; Molecular and cellular biology; Multiprotein Complexes - chemistry; Multiprotein Complexes - metabolism; Nuclear Proteins - metabolism; Protein Binding; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases - metabolism; Species Specificity; Static Electricity
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2012.09.012

To ensure equal chromosome segregation during mitosis, the macromolecular kinetochore must remain attached to depolymerizing microtubules, which drive chromosome movements. How kinetochores associate with depolymerizing microtubules, which undergo dramatic structural changes forming curved protofilaments, has yet to be defined in vertebrates. Here, we demonstrate that the conserved kinetochore-localized Ska1 complex tracks with depolymerizing microtubule ends and associates with both the microtubule lattice and curved protofilaments. In contrast, the Ndc80 complex, a central player in the kinetochore-microtubule interface, binds only to the straight microtubule lattice and lacks tracking activity. We demonstrate that the Ska1 complex imparts its tracking capability to the Ndc80 complex. Finally, we present a structure of the Ska1 microtubule-binding domain that reveals its interaction with microtubules and its regulation by Aurora B. This work defines an integrated kinetochore-microtubule interface formed by the Ska1 and Ndc80 complexes that associates with depolymerizing microtubules, potentially by interacting with curved microtubule protofilaments. [Display omitted] ► The Ska1 complex tracks with depolymerizing microtubules ► The Ska1 complex associates with curved protofilament structures ► The Ndc80 and Ska1 complexes bind to and track microtubules synergistically ► The Ska1 complex microtubule-binding domain has a winged-helix structure Microtubule depolymerization-driven chromosome movements are essential for chromosome segregation. Schmidt et al. demonstrate that the human Ska1 and Ndc80 complexes form an integrated kinetochore-microtubule interface that tracks depolymerizing microtubule ends. The Ska1 complex utilizes a winged-helix domain to associate with both the straight microtubule lattice and curved protofilament structures.