CLASPs are conserved microtubule plus-end–tracking proteins that suppress microtubule catastrophes and independently localize to kinetochores during mitosis. Thus, CLASPs are ideally positioned to regulate kinetochore–microtubule dynamics required for chromosome segregation fidelity, but the underlying mechanism remains unknown. Here, we found that human CLASP2 exists predominantly as a monomer in solution, but it can self-associate through its C-terminal kinetochore-binding domain. Kinetochore localization was independent of self-association, and driving monomeric CLASP2 to kinetochores fully rescued normal kinetochore–microtubule dynamics, while partially sustaining mitosis. CLASP2 kinetochore localization, recognition of growing microtubule plus-ends through EB–protein interaction, and the ability to associate with curved microtubule protofilaments through TOG2 and TOG3 domains independently sustained normal spindle length, timely spindle assembly checkpoint satisfaction, chromosome congression, and faithful segregation. Measurements of kinetochore–microtubule half-life and poleward flux revealed that CLASP2 regulates kinetochore–microtubule dynamics by integrating distinctive microtubule-binding properties at the kinetochore–microtubule interface. We propose that kinetochore CLASP2 suppresses microtubule depolymerization and detachment by binding to curved protofilaments at microtubule plus-ends.

中文翻译：

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CLASP2 与弯曲微管尖端的结合可促进通量并稳定动粒附着

CLASP 是保守的微管正端跟踪蛋白，可抑制微管灾难并在有丝分裂过程中独立定位于动粒。因此，CLASP 非常适合调节染色体分离保真度所需的动粒-微管动力学，但其潜在机制仍不清楚。在这里，我们发现人类 CLASP2 主要以单体形式存在于溶液中，但它可以通过其 C 端动粒结合域进行自缔合。着丝粒定位独立于自关联，将单体 CLASP2 驱动到着丝粒完全挽救了正常的着丝粒-微管动力学，同时部分维持了有丝分裂。CLASP2着丝粒定位、通过EB-蛋白质相互作用识别生长的微管正端，以及通过TOG2和TOG3结构域与弯曲微管原丝关联的能力，独立地维持了正常的纺锤体长度、及时的纺锤体组装检查点满足、染色体会聚和忠实的分离。着丝粒-微管半衰期和向极通量的测量表明，CLASP2 通过在着丝粒-微管界面整合独特的微管结合特性来调节着丝粒-微管动力学。我们提出动粒 CLASP2 通过与微管正端的弯曲原丝结合来抑制微管解聚和脱离。