Augmin prevents merotelic attachments by promoting proper arrangement of bridging and kinetochore fibers

The human mitotic spindle is made of microtubules nucleated at centrosomes, at kinetochores, and from pre-existing microtubules by the augmin complex. However, it is unknown how the augmin-mediated nucleation affects distinct microtubule classes and thereby mitotic fidelity. Here we use superresolution microscopy to analyze the previously indistinguishable microtubule arrangements within the crowded metaphase plate area and demonstrate that augmin is vital for the formation of uniformly arranged parallel units consisting of sister kinetochore fibers connected by a bridging fiber. This ordered geometry helps both prevent and resolve merotelic attachments. Whereas augmin-nucleated bridging fibers prevent merotelic attachments by creating a nearly parallel and highly bundled microtubule arrangement unfavorable for creating additional attachments, augmin-nucleated k-fibers produce robust force required to resolve errors during anaphase. STED microscopy revealed that bridging fibers were imp...

人类有丝分裂纺锤体由三类微管构成：在中心体（centrosome）处成核的微管、在动粒（kinetochore）处成核的微管，以及由奥格明复合物（augmin complex）从预存微管中诱导成核形成的微管。然而，目前尚不明确奥格明复合物介导的微管成核过程如何影响不同类别的微管，进而对有丝分裂保真度产生影响。本研究采用超分辨率显微镜（superresolution microscopy）技术，对拥挤的赤道板（metaphase plate）区域内此前难以分辨的微管排布进行分析，证实奥格明复合物对于形成由桥纤维（bridging fiber）连接的姐妹动粒纤维（sister kinetochore fiber）所构成的均匀排列平行单元至关重要。这种有序的几何结构既可预防也可解决牵错动粒附着（merotelic attachment）问题。奥格明复合物成核形成的桥纤维可通过构建近乎平行且高度成束的微管排布，抑制额外附着的形成，从而预防牵错动粒附着；而奥格明复合物成核形成的动粒纤维（k-fiber）则可产生有丝分裂后期（anaphase）纠正错误所需的稳定拉力。受激发射损耗显微镜（STED microscopy）成像显示，桥纤维的……