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SKAP与微管的结合可降低动粒-微管界面处的摩擦力,并在受力情况下增强附着稳定性。

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

作者信息

Rosas-Salvans Miquel, Rux Caleb, Das Moumita, Dumont Sophie

机构信息

Dept of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, CA.

Bioengineering Graduate Program, UCSF-UCB, San Francisco, CA.

出版信息

bioRxiv. 2024 Aug 8:2024.08.08.607154. doi: 10.1101/2024.08.08.607154.

Abstract

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.

摘要

动粒将染色体与纺锤体微管相连,以驱动细胞分裂时的染色体分离。我们最近发现,与微管结合的动粒复合物Astrin-SKAP在哺乳动物动粒-微管界面处降低而非增加摩擦力。其作用方式尚不清楚。Astrin-SKAP可能会影响其他动粒复合物与微管的结合方式,从而降低它们沿微管的摩擦力,或者它自身与微管结合的亲和力与其他附着因子相似,但摩擦力更低。我们使用无法与微管结合的SKAP突变体、实时成像和激光消融技术,表明SKAP与微管的结合对于姐妹动粒协调、界面处的力消散以及附着对力变化的响应至关重要。此外,我们表明SKAP与微管的结合对于防止在纺锤体力和微针产生的力作用下染色体分离至关重要。总之,我们的研究结果表明,SKAP与微管的结合可降低动粒摩擦力,并在受力情况下增加附着响应性和稳定性。我们提出,在微管上具有高滑动摩擦力和低滑动摩擦力的复合物,形成一个机械性质不同的界面,是在受力情况下维持稳固附着从而实现精确分离的关键。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad2a/11326240/1cce6cb6aaa2/nihpp-2024.08.08.607154v1-f0001.jpg

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