SKAP binding to microtubules reduces friction at the kinetochore-microtubule interface and increases attachment stability under force

Data associated to the paper "The Astrin-SKAP Complex Reduces Friction at the Kinetochore-Microtubule Interface", Rosas-Salvans et al., Current Biology, DOI: 10.1016/j.cub.2022.04.061.

Here we include the data used for the figures in this paper (files are created and must be opened using GraphPad-Prism or Microsoft Excel). The raw data and Phyton code used for the kinetochore oscillations analysis can be found at the following link: https://github.com/miquelrosassalvans/Rosas-Salvans-2024-kinetochore-oscillations

Summary of the work: The kinetochore links chromosomes to spindle microtubules to drive chromosome segregation at cell division. We recently uncovered that the kinetochore complex Astrin-SKAP, which binds microtubules, reduces rather than increases friction at the mammalian kinetochore-microtubule interface. How it does so is not known. Astrin-SKAP could affect how other kinetochore complexes bind microtubules, reducing their friction along microtubules, or it could itself bind microtubules with similar affinity but lower friction than other attachment factors. Using SKAP mutants unable to bind microtubules, live imaging and laser ablation, we show that SKAP’s microtubule binding is essential for sister kinetochore coordination, force dissipation at the interface and attachment responsiveness to force changes. Further, we show that SKAP’s microtubule binding is essential to prevent chromosome detachment under both spindle forces and microneedle-generated forces. Together, our findings indicate that SKAP’s microtubule binding reduces kinetochore friction and increases attachment responsiveness and stability under force. We propose that having complexes with both high and low sliding friction on microtubules, making a mechanically heterogeneous interface, is key to maintaining robust attachments under force and thus accurate segregation.

本数据集关联论文《Astrin-SKAP复合物降低着丝粒-微管界面摩擦》（Rosas-Salvans等，发表于*Current Biology*，DOI: 10.1016/j.cub.2022.04.061）。

本数据集收录该论文配图所用的全部数据，文件需使用GraphPad-Prism或Microsoft Excel打开。用于着丝粒（kinetochore）振荡分析的原始数据及Python代码，可通过以下链接获取：https://github.com/miquelrosassalvans/Rosas-Salvans-2024-kinetochore-oscillations

研究概述：着丝粒可将染色体连接至纺锤体微管，介导细胞分裂过程中的染色体分离。我们近期发现，能够结合微管的着丝粒复合物Astrin-SKAP，反而会降低哺乳动物细胞着丝粒-微管界面的摩擦，而非升高该界面摩擦，具体作用机制仍有待阐明。Astrin-SKAP可能通过两种途径发挥作用：一是影响其他着丝粒复合物与微管的结合方式，降低其沿微管滑动时的摩擦；二是自身以与其他附着因子相近的结合亲和力与微管结合，但产生更低的摩擦。我们通过构建无法结合微管的SKAP突变体、结合活细胞成像与激光消融实验，证实SKAP的微管结合能力对于姐妹着丝粒的协同调控、界面处的力耗散以及附着结构对应力变化的响应性均不可或缺。此外，我们还证明，SKAP的微管结合能力可防止染色体在纺锤体拉力及显微针施加的拉力下发生脱离。综上，本研究结果表明，SKAP的微管结合功能可降低着丝粒摩擦，提升附着结构对应力的响应性与受力稳定性。我们据此提出假说：若微管表面同时存在高、低滑动摩擦的复合物，形成力学异质性界面，将有助于在受力状态下维持稳定的染色体附着，进而保障精准的染色体分离。