Human Ska complex and Ndc80 complex interact to form a load-bearing assembly that strengthens kinetochore-microtubule attachments.
Human Ska complex and Ndc80 complex interact to form a load-bearing assembly that strengthens kinetochore-microtubule attachments.
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DOI：
10.1073/pnas.1718553115
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发表时间：
2018-03-13
影响因子：
11.1
通讯作者：
Davis TN
中科院分区：
文献类型：
--
作者：
Helgeson LA;Zelter A;Riffle M;MacCoss MJ;Asbury CL;Davis TN
微管是动态的管状结构，在细胞分裂过程中驱动复制染色体的分离。斯卡复合体是分子机器的一部分，它在染色体和微管末端之间形成受力连接。Ska复合物的消耗破坏了这些连接并破坏了细胞分裂。Ska复合物结合微管，但不知道它是否直接在微管上保持力或间接稳定连接。在这里，我们表明，斯卡复杂的微管末端和组装与另一个微管结合组件，Ndc 80复合物，以加强其承受力的能力，使一个直接的力轴承连接。我们的研究结果表明，Ska和Ndc 80复合物一起工作，以维持染色体和微管末端之间的连接。染色体的精确分离依赖于着丝粒的受力能力，以将染色体牢固地附着到动态微管尖端。人Ska复合物和Ndc 80复合物是结合微管的外动粒组分，并且是体内完全稳定动粒-微管附着所需的。虽然纯化的Ska复合物的轨道与拆卸微管提示，它仍然不清楚是否Ska复合物微管相互作用是足够强，使一个显着的贡献，激动剂微管耦合。或者，斯卡复合物可能会影响动粒偶联间接，通过招募磷酸调节因子。使用光镊，我们表明，斯卡复杂本身承担的微管尖端上的负载，加强Ndc 80复合物为基础的尖端附件，并增加所附的微管尖端的开关动力学。交联质谱表明Ska复合物通过Ska 3非结构化C-末端区域和每个Ndc 80复合物亚基的卷曲螺旋区域之间的相互作用直接结合Ndc 80复合物。Ska复合物微管结合结构域或Ska 3 C末端的缺失防止Ska复合物加强基于Ndc 80复合物的附着。总之，我们的研究结果表明，SKA复合物可以直接加强激动剂微管界面和调节微管尖端动力学之间形成一个额外的连接Ndc 80复合物和微管。
Microtubules are dynamic, tube-like structures that drive the segregation of duplicated chromosomes during cell division. The Ska complex is part of a molecular machine that forms force-bearing connections between chromosomes and microtubule ends. Depletion of the Ska complex destabilizes these connections and disrupts cell division. The Ska complex binds microtubules, but it is unknown whether it directly holds force at microtubules or indirectly stabilizes the connections. Here, we show that the Ska complex makes a direct force-bearing linkage with microtubule ends and assembles with another microtubule binding component, the Ndc80 complex, to strengthen its ability to withstand force. Our results suggest that the Ska and Ndc80 complexes work together to maintain the connections between chromosomes and microtubule ends. Accurate segregation of chromosomes relies on the force-bearing capabilities of the kinetochore to robustly attach chromosomes to dynamic microtubule tips. The human Ska complex and Ndc80 complex are outer-kinetochore components that bind microtubules and are required to fully stabilize kinetochore–microtubule attachments in vivo. While purified Ska complex tracks with disassembling microtubule tips, it remains unclear whether the Ska complex–microtubule interaction is sufficiently strong to make a significant contribution to kinetochore–microtubule coupling. Alternatively, Ska complex might affect kinetochore coupling indirectly, through recruitment of phosphoregulatory factors. Using optical tweezers, we show that the Ska complex itself bears load on microtubule tips, strengthens Ndc80 complex-based tip attachments, and increases the switching dynamics of the attached microtubule tips. Cross-linking mass spectrometry suggests the Ska complex directly binds Ndc80 complex through interactions between the Ska3 unstructured C-terminal region and the coiled-coil regions of each Ndc80 complex subunit. Deletion of the Ska complex microtubule-binding domain or the Ska3 C terminus prevents Ska complex from strengthening Ndc80 complex-based attachments. Together, our results indicate that the Ska complex can directly strengthen the kinetochore–microtubule interface and regulate microtubule tip dynamics by forming an additional connection between the Ndc80 complex and the microtubule.
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NDC80尾部的去磷酸化稳定了KineTochore-Microubulule附件，通过SKA络合物。
影响因子：
11.8
作者：
Cheerambathur DK;Prevo B;Hattersley N;Lewellyn L;Corbett KD;Oegema K;Desai A
通讯作者：
Desai A
影响因子：
11.8
作者：
Schmidt, Jens C.;Arthanari, Haribabu;Boeszoermenyi, Andras;Dashkevich, Natalia M.;Wilson-Kubalek, Elizabeth M.;Monnier, Nilah;Markus, Michelle;Oberer, Monika;Milligan, Ron A.;Bathe, Mark;Wagner, Gerhard;Grishchuk, Ekaterina L.;Cheeseman, Iain M.
通讯作者：
Cheeseman, Iain M.
影响因子：
4
作者：
Raaijmakers, Jonne A.;Tanenbaum, Marvin E.;Medema, Rene H.
通讯作者：
Medema, Rene H.
影响因子：
16
作者：
Jeyaprakash, A. Arockia;Santamaria, Anna;Conti, Elena
通讯作者：
Conti, Elena
DOI：
10.1083/jcb.200909005
发表时间：
2010-03-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jaqaman K;King EM;Amaro AC;Winter JR;Dorn JF;Elliott HL;McHedlishvili N;McClelland SE;Porter IM;Posch M;Toso A;Danuser G;McAinsh AD;Meraldi P;Swedlow JR
通讯作者：
Swedlow JR