SKAP 与微管的结合可减少动子心轴与微管界面的摩擦,并提高受力时的附着稳定性

bioRxiv Pub Date : 2024-08-08 DOI:10.1101/2024.08.08.607154
Miquel Rosas-Salvans, Caleb J. Rux, Moumita Das, Sophie Dumont
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摘要

动核将染色体与纺锤体微管连接起来,在细胞分裂时驱动染色体分离。我们最近发现,与微管结合的动点核心复合体 Astrin-SKAP 可减少而不是增加哺乳动物动点核心与微管界面的摩擦。它是如何做到这一点的尚不清楚。Astrin-SKAP可能会影响其他动点核复合物与微管的结合方式,从而减少它们在微管上的摩擦力,或者它本身也能以类似的亲和力结合微管,但摩擦力低于其他附着因子。利用无法结合微管的 SKAP 突变体、活体成像和激光烧蚀,我们发现 SKAP 的微管结合对于姊妹动核的协调、界面上的力耗散以及附着对力变化的响应至关重要。此外,我们还发现,SKAP的微管结合对于防止染色体在主轴力和微针力作用下脱落至关重要。总之,我们的研究结果表明,SKAP的微管结合减少了动点摩擦,提高了附着反应能力和受力时的稳定性。我们认为,微管上既有高滑动摩擦力也有低滑动摩擦力的复合物,从而形成一个机械异质界面,是在力的作用下保持稳健附着从而准确分离的关键。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SKAP binding to microtubules reduces friction at the kinetochore-microtubule interface and increases attachment stability under force
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.
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