Dynamic crotonylation of EB1 by TIP60 ensures accurate spindle positioning in mitosis

Nat Chem Biol. 2021 Dec;17(12):1314-1323. doi: 10.1038/s41589-021-00875-7.

Xiaoyu Song ^# ¹ ², Fengrui Yang ^# ¹ ², Xu Liu ^# ¹ ², Peng Xia ^# ¹, Wu Yin ¹, Zhikai Wang ¹ ², Yong Wang ³, Xiao Yuan ¹ ⁴, Zhen Dou ¹, Kai Jiang ³, Mingming Ma ¹, Bing Hu ¹, Rui Zhang ⁵, Chao Xu ¹, Zhiyong Zhang ¹, Ke Ruan ¹, Ruijun Tian ⁴, Lin Li ⁶, Tao Liu ⁷, Donald L Hill ⁸, Jianye Zang ⁹, Xing Liu ¹⁰ ¹¹, Jinsong Li ¹², Jinke Cheng ¹³, Xuebiao Yao ¹⁴ ¹⁵ ¹⁶

Affiliations

1 MOE Key Laboratory for Cellular Dynamics and Hefei National Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
2 Keck Center for Organoids Plasticity, Morehouse School of Medicine, Atlanta, GA, USA.
3 Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, China.
4 Department of Chemistry, Southern University of Science and Technology, Shenzhen, China.
5 Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
6 Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
7 State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.
8 Comprehensive Cancer Center, University of Alabama, Birmingham, AL, USA.
9 MOE Key Laboratory for Cellular Dynamics and Hefei National Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China. zangjy@ustc.edu.cn.
10 MOE Key Laboratory for Cellular Dynamics and Hefei National Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China. xing1017@ustc.edu.cn.
11 Keck Center for Organoids Plasticity, Morehouse School of Medicine, Atlanta, GA, USA. xing1017@ustc.edu.cn.
12 Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China. jsli@sibcb.ac.cn.
13 Department of Biochemistry, Shanghai Jiaotong University School of Medicine, Shanghai, China. jkcheng@shsmu.edu.cn.
14 MOE Key Laboratory for Cellular Dynamics and Hefei National Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China. yaoxb@ustc.edu.cn.
15 Keck Center for Organoids Plasticity, Morehouse School of Medicine, Atlanta, GA, USA. yaoxb@ustc.edu.cn.
16 Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China. yaoxb@ustc.edu.cn.
# Contributed equally.

PMID: 34608293 DOI: 10.1038/s41589-021-00875-7

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.

Name
Email *

	Sorry, but the email address you supplied was invalid.