title: The kinetochore-bound Ska1 complex tracks depolymerizing microtubules and binds to curved protofilaments.
abstract: 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.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Schmidt
authors.forename: Haribabu
authors.initials: H
authors.lastname: Arthanari
authors.forename: Andras
authors.initials: A
authors.lastname: Boeszoermenyi
authors.forename: Natalia M
authors.initials: NM
authors.lastname: Dashkevich
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Wilson-Kubalek
authors.forename: Nilah
authors.initials: N
authors.lastname: Monnier
authors.forename: Michelle
authors.initials: M
authors.lastname: Markus
authors.forename: Monika
authors.initials: M
authors.lastname: Oberer
authors.forename: Ron A
authors.initials: RA
authors.lastname: Milligan
authors.forename: Mark
authors.initials: M
authors.lastname: Bathe
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner
authors.forename: Ekaterina L
authors.initials: EL
authors.lastname: Grishchuk
authors.forename: Iain M
authors.initials: IM
authors.lastname: Cheeseman
mesh_terms: D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D003598:Cytoskeletal Proteins; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008938:Mitosis; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013045:Species Specificity; D055672:Static Electricity
chemical_list: D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; D046912:Multiprotein Complexes; C120529:NDC80 protein, human; D009687:Nuclear Proteins; C516427:SKA1 protein, human; C000602228:ska-1 protein, C elegans; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases