The Human Kinetochore Ska1 Complex Facilitates Microtubule Depolymerization-Coupled Motility

• Published in: Developmental cell 2009-03, Vol.16 (3), p.374-385
• Main Authors: Welburn, Julie P.I., Grishchuk, Ekaterina L., Backer, Chelsea B., Wilson-Kubalek, Elizabeth M., Yates, John R., Cheeseman, Iain M.
• Format: Article
• Language: English
• Subjects: Base Sequence; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell Line; Cell physiology; Cell structures and functions; CELLBIO; Chromosomal Proteins, Non-Histone - antagonists & inhibitors; Chromosomal Proteins, Non-Histone - chemistry; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - physiology; Chromosome Segregation - physiology; Cytoskeleton, cytoplasm. Intracellular movements; Fundamental and applied biological sciences. Psychology; Fungal Proteins - chemistry; Fungal Proteins - physiology; Humans; Kinetochores - physiology; Microscopy, Electron, Transmission; Microspheres; Microtubule-Associated Proteins - chemistry; Microtubule-Associated Proteins - physiology; Microtubules - physiology; Microtubules - ultrastructure; Mitosis - physiology; Models, Biological; Molecular and cellular biology; Movement - physiology; Multiprotein Complexes; Protein Binding; Protein Subunits; RNA, Small Interfering - genetics; Species Specificity
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2009.01.011

Mitotic chromosome segregation requires that kinetochores attach to microtubule polymers and harness microtubule dynamics to drive chromosome movement. In budding yeast, the Dam1 complex couples kinetochores with microtubule depolymerization. However, a metazoan homolog of the Dam1 complex has not been identified. To identify proteins that play a corresponding role at the vertebrate kinetochore-microtubule interface, we isolated a three subunit human Ska1 complex, including the previously uncharacterized protein Rama1 that localizes to the outer kinetochore and spindle microtubules. Depletion of Ska1 complex subunits severely compromises proper chromosome segregation. Reconstituted Ska1 complex possesses two separable biochemical activities: direct microtubule binding through the Ska1 subunit, and microtubule-stimulated oligomerization imparted by the Rama1 subunit. The full Ska1 complex forms assemblies on microtubules that can facilitate the processive movement of microspheres along depolymerizing microtubules. In total, these results demonstrate a critical role for the Ska1 complex in interacting with dynamic microtubules at the outer kinetochore.