Demidov Vladimir M, Gonchar Ivan V, Tripathy Suvranta K, Ataullakhanov Fazly I, Grishchuk Ekaterina L
Department of Physiology, University of Pennsylvania, Philadelphia, PA, USA.
Sci Adv. 2025 Sep 5;11(36):eadx0005. doi: 10.1126/sciadv.adx0005. Epub 2025 Sep 3.
Chromosome motion at spindle microtubule plus ends relies on dynamic molecular bonds between kinetochores and proximal microtubule walls. Under opposing forces, kinetochores move bidirectionally along these walls while remaining near the ends, yet how continuous wall sliding occurs without end detachment remains unclear. Using ultrafast force-clamp spectroscopy, we show that single Ndc80 complexes, the primary microtubule-binding kinetochore component, exhibit processive, bidirectional sliding. Plus end-directed forces induce a mobile catch bond in Ndc80, increasing frictional resistance and restricting sliding toward the tip. Conversely, forces pulling Ndc80 away from the plus end trigger mobile slip-bond behavior, facilitating sliding. This dual behavior arises from force-dependent modulation of the Nuf2 calponin-homology domain's microtubule binding, identifying this subunit as a friction regulator. We propose that Ndc80's ability to modulate sliding friction provides the mechanistic basis for the kinetochore's end coupling, enabling its slip-clutch behavior.
染色体在纺锤体微管正端的运动依赖于动粒与近端微管壁之间的动态分子键。在相反的力作用下,动粒沿着这些壁双向移动,同时仍靠近微管末端,但尚不清楚在不发生末端脱离的情况下,连续的壁滑动是如何发生的。利用超快力钳光谱技术,我们发现单个Ndc80复合物(主要的微管结合动粒组分)表现出持续的双向滑动。微管正端定向的力在Ndc80中诱导出一种可移动的捕获键,增加摩擦阻力并限制向微管末端的滑动。相反,将Ndc80从微管正端拉开的力触发可移动的滑键行为,促进滑动。这种双重行为源于Nuf2钙调蛋白同源结构域与微管结合的力依赖性调节,确定该亚基为摩擦调节剂。我们提出,Ndc80调节滑动摩擦的能力为动粒的末端耦合提供了机制基础,使其具有滑-离合行为。