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

被引:167
作者
Schmidt, Jens C. [1 ,2 ]
Arthanari, Haribabu [4 ]
Boeszoermenyi, Andras [4 ,7 ]
Dashkevich, Natalia M. [6 ]
Wilson-Kubalek, Elizabeth M. [5 ]
Monnier, Nilah [3 ]
Markus, Michelle [4 ]
Oberer, Monika [7 ]
Milligan, Ron A. [5 ]
Bathe, Mark [3 ]
Wagner, Gerhard [4 ]
Grishchuk, Ekaterina L. [6 ]
Cheeseman, Iain M. [1 ,2 ]
机构
[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[2] MIT, Dept Biol, Cambridge, MA 02142 USA
[3] MIT, Dept Biol Engn, Cambridge, MA 02142 USA
[4] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
[5] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
[6] Univ Penn, Dept Physiol, Perelman Sch Med, Philadelphia, PA 19104 USA
[7] Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria
基金
奥地利科学基金会;
关键词
DASH COMPLEX; IN-VITRO; AURORA B; ATTACHMENT; DYNAMICS; TUBULIN; NMR; INTERFACE; COMPONENT; PROTEINS;
D O I
10.1016/j.devcel.2012.09.012
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:968 / 980
页数:13
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