The dynein adaptor Hook2 plays essential roles in mitotic progression and cytokinesis
The dynein adaptor Hook2 plays essential roles in mitotic progression and cytokinesis
复制标题
DOI：
10.1083/jcb.201804183
复制
发表时间：
2019-03-01
影响因子：
7.8
通讯作者：
Sharma, Mahak
中科院分区：
文献类型：
--
作者：
Dwivedi, Devashish;Kumari, Amrita;Sharma, Mahak
钩蛋白是进化上保守的动力蛋白衔接子，可促进高度进行性动力蛋白-动力蛋白运动复合体的组装。哺乳动物表达三种Hook旁系同源物，即Hook 1、Hook 2和Hook 3，它们具有不同的亚细胞定位和不同的细胞功能。在这里，我们证明了钩2结合，并促进动力蛋白-动力蛋白组装，特别是在有丝分裂。在G2晚期，Hook 2介导动力蛋白-动力蛋白定位于核膜（NE），这是中心体锚定到NE所需的。独立的结合动力蛋白，钩2调节微管成核的中心体，因此，钩2耗尽细胞减少星形微管和纺锤体定位缺陷。除了中心体，Hook 2定位于并招募动力蛋白和动力肌动蛋白到中央纺锤体。Dynactin依赖性靶向centralspindlin复合物的中间区被废除后，Hook 2耗尽;因此，Hook 2耗尽导致胞质分裂失败。我们发现，斑马鱼Hook 2同源物促进动力蛋白-动力肌动蛋白协会，是必不可少的斑马鱼早期发育。总之，这些结果表明，Hook 2介导的动力蛋白-dynactin复合物的组装和调节有丝分裂的进展和胞质分裂。
Hook proteins are evolutionarily conserved dynein adaptors that promote assembly of highly processive dynein-dynactin motor complexes. Mammals express three Hook paralogs, namely Hook1, Hook2, and Hook3, that have distinct subcellular localizations and expectedly, distinct cellular functions. Here we demonstrate that Hook2 binds to and promotes dynein-dynactin assembly specifically during mitosis. During the late G2 phase, Hook2 mediates dynein-dynactin localization at the nuclear envelope (NE), which is required for centrosome anchoring to the NE. Independent of its binding to dynein, Hook2 regulates microtubule nucleation at the centrosome; accordingly, Hook2-depleted cells have reduced astral microtubules and spindle positioning defects. Besides the centrosome, Hook2 localizes to and recruits dynactin and dynein to the central spindle. Dynactin-dependent targeting of centralspindlin complex to the midzone is abrogated upon Hook2 depletion; accordingly, Hook2 depletion results in cytokinesis failure. We find that the zebrafish Hook2 homologue promotes dynein-dynactin association and was essential for zebrafish early development. Together, these results suggest that Hook2 mediates assembly of the dynein-dynactin complex and regulates mitotic progression and cytokinesis.