WDR62 is a microcephaly-related, microtubule (MT)-associated protein (MAP) that localizes to the spindle pole and regulates spindle organization, but the underlying mechanisms remain elusive. Here, we show that WDR62 regulates spindle dynamics by recruiting katanin to the spindle pole and further reveal a TPX2–Aurora A–WDR62–katanin axis in cells. By combining cellular and in vitro experiments, we demonstrate that WDR62 shows preference for curved segments of dynamic GDP-MTs, as well as GMPCPP- and paclitaxel-stabilized MTs, suggesting that it recognizes extended MT lattice. Consistent with this property, WDR62 alone is inefficient in recruiting katanin to GDP-MTs, while WDR62 complexed with TPX2/Aurora A can potently promote katanin-mediated severing of GDP-MTs in vitro. In addition, the MT-binding affinity of WDR62 is autoinhibited through JNK phosphorylation-induced intramolecular interaction. We propose that WDR62 is an atypical MAP and functions as an adaptor protein between its recruiting factor TPX2/Aurora A and the effector katanin to orchestrate the regulation of spindle dynamics.

中文翻译：

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WDR62 作为 TPX2/Aurora A 和剑蛋白之间的衔接蛋白调节纺锤体动力学

WDR62 是一种与小头畸形相关的微管 (MT) 相关蛋白 (MAP)，定位于纺锤体极并调节纺锤体组织，但其潜在机制仍不清楚。在这里，我们证明 WDR62 通过将剑蛋白募集到纺锤体极来调节纺锤体动力学，并进一步揭示了细胞中的 TPX2-Aurora A-WDR62-剑蛋白轴。通过结合细胞和体外实验，我们证明 WDR62 对动态 GDP-MT 的弯曲段以及 GMPCPP 和紫杉醇稳定的 MT 表现出偏好，表明它识别扩展的 MT 晶格。与此特性一致，单独的 WDR62 在将剑蛋白募集到 GDP-MT 方面效率较低，而 WDR62 与 TPX2/Aurora A 复合可以在体外有效促进剑蛋白介导的 GDP-MT 切断。此外，WDR62 的 MT 结合亲和力通过 JNK 磷酸化诱导的分子内相互作用被自动抑制。我们认为 WDR62 是一种非典型 MAP，作为其募集因子 TPX2/Aurora A 和效应子剑蛋白之间的衔接蛋白来协调纺锤体动力学的调节。