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

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Developmental Cell (Impact Factor: 10.37). 10/2012; 23(5). DOI: 10.1016/j.devcel.2012.09.012
Source: PubMed

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.

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    • "Overexpression of AURK-A has been shown to be associated with aneuploidy, chromosome instablity, tumorigenic transformation and progression in mammalian cells (Bischoff et al. 1998; revised in Gómez-López et al. 2014). AURK-B has been shown to regulate SKA1 (Schmidt et al. 2012). KIF11 is a protein required from prophase until metaphase which participates in spindle assembly, centrosome separation, post-mitotic centrosome movement and bipolar spindle formation. "
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    • "Notably, spindle and kinetochore-associated protein complexes have several key properties, and play an important role in coupling chromosome movement to microtubule depolymerization [11,12]. Spindle and kinetochore associated complex subunit 1 (SKA1) is a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation [13,14]. Depletion of SKA1 proteins results in sparse microtubule arrays that often exhibited twisted or bent spindles. "
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    • "To date, all the Ndc80 loop-interacting proteins identified have no reported microtubule depolymerising activity. Although the Dam1 and Ska complexes have been shown to track on the plus end of depolymerising microtubules and the TOG proteins are in fact microtubule polymerases, it remains enigmatic as to how microtubule depolymerisation per se is directionally driven during anaphase A [16,17]. It should also be of note that whether the Dam1 and the Ska complexes interact with the loop remains to be established [16,18]. "
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