| Literature DB >> 34608293 |
Xiaoyu Song1,2, Fengrui Yang1,2, Xu Liu1,2, Peng Xia1, Wu Yin1, Zhikai Wang1,2, Yong Wang3, Xiao Yuan1,4, Zhen Dou1, Kai Jiang3, Mingming Ma1, Bing Hu1, Rui Zhang5, Chao Xu1, Zhiyong Zhang1, Ke Ruan1, Ruijun Tian4, Lin Li6, Tao Liu7, Donald L Hill8, Jianye Zang9, Xing Liu10,11, Jinsong Li12, Jinke Cheng13, Xuebiao Yao14,15,16.
Abstract
Spindle position control is essential for cell fate determination and organogenesis. Early studies indicate the essential role of the evolutionarily conserved Gαi/LGN/NuMA network in spindle positioning. However, the regulatory mechanisms that couple astral microtubules dynamics to the spindle orientation remain elusive. Here we delineated a new mitosis-specific crotonylation-regulated astral microtubule-EB1-NuMA interaction in mitosis. EB1 is a substrate of TIP60, and TIP60-dependent crotonylation of EB1 tunes accurate spindle positioning in mitosis. Mechanistically, TIP60 crotonylation of EB1 at Lys66 forms a dynamic link between accurate attachment of astral microtubules to the lateral cell cortex defined by NuMA-LGN and fine tune of spindle positioning. Real-time imaging of chromosome movements in HeLa cells expressing genetically encoded crotonylated EB1 revealed the importance of crotonylation dynamics for accurate control of spindle orientation during metaphase-anaphase transition. These findings delineate a general signaling cascade that integrates protein crotonylation with accurate spindle positioning for chromosome stability in mitosis.Entities:
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Year: 2021 PMID： 34608293 DOI： 10.1038/s41589-021-00875-7
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040