A dynein independent role of Tctex-1 at the kinetochore

Dynein light chains are accessory subunits of the cytoplasmic dynein complex, a minus-end directed microtubule motor. Here, we demonstrate that the dynein light chain Tctex-1 associates with unattached kinetochores and is essential for accurate chromosome segregation. Tctex-1 knockdown in cells does not affect the localization and function of dynein at the kinetochore, but produces a prolonged mitotic arrest with a few misaligned chromosomes, which are subsequently missegregated during anaphase. This function is independent of Tctex-1's association with dynein. The kinetochore localization of Tctex-1 is independent of the ZW10-dynein pathway, but requires the Ndc80 complex. Thus, our findings reveal a dynein independent role of Tctex-1 at the kinetochore to enhance the stability of kinetochore-microtubule attachment.

动力蛋白轻链（Dynein Light Chains）是细胞质动力蛋白复合体（cytoplasmic dynein complex）的附属亚基，该复合体属于一类负端导向的微管马达蛋白（minus-end directed microtubule motor）。本研究证实，动力蛋白轻链Tctex-1可定位于未附着微管的着丝粒（unattached kinetochores），且对精确的染色体分离（chromosome segregation）至关重要。对细胞开展Tctex-1敲低实验后，并不会影响动力蛋白在着丝粒处的定位与功能，但会引发细胞出现长时间的有丝分裂阻滞，并伴随少量染色体排列紊乱，这些紊乱的染色体后续会在分裂后期发生错误分离。该功能并不依赖Tctex-1与动力蛋白的结合。Tctex-1在着丝粒处的定位不依赖ZW10-动力蛋白通路，但需要Ndc80复合体（Ndc80 Complex）。综上，本研究结果揭示了Tctex-1在着丝粒处不依赖动力蛋白的新功能，即增强着丝粒-微管附着的稳定性。