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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aurora Kinase B
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Aurora Kinases
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Caenorhabditis elegans Proteins / antagonists & inhibitors
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Chromosomal Proteins, Non-Histone / antagonists & inhibitors
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Chromosomal Proteins, Non-Histone / chemistry
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Chromosomal Proteins, Non-Histone / genetics
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Chromosomal Proteins, Non-Histone / metabolism*
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Chromosome Segregation
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Cytoskeletal Proteins
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HeLa Cells
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Humans
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Kinetochores / metabolism*
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Microtubules / metabolism*
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Microtubules / ultrastructure
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Mitosis
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Models, Molecular
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Multiprotein Complexes / chemistry
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Multiprotein Complexes / metabolism
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Nuclear Proteins / metabolism
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Protein Binding
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Protein Serine-Threonine Kinases / metabolism
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Protein Structure, Tertiary
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Species Specificity
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Static Electricity
Substances
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Caenorhabditis elegans Proteins
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Chromosomal Proteins, Non-Histone
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Cytoskeletal Proteins
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Multiprotein Complexes
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NDC80 protein, human
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Nuclear Proteins
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SKA1 protein, human
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ska-1 protein, C elegans
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AURKB protein, human
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Aurora Kinase B
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Aurora Kinases
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Protein Serine-Threonine Kinases