Organization of microtubule plus-end dynamics by phase separation in mitosis  

作　　者：Fengrui Yang Mingrui Ding Xiaoyu Song Fang Chen Tongtong Yang Chunyue Wang Chengcheng Hu Qing Hu Yihan Yao Shihao Du Phil YYao Peng Xia Gregory Adams Jr Chuanhai Fu Shengqi Xiang Dan Liu Zhikai Wang Kai Yuan Xing Liu 

机构地区：[1]MOE Key Laboratory for Membraneless Organelles&Cellular Dynamics,Hefei National Research Center for Cross-disciplinary Sciences,Center for Advanced Interdisciplinary Science and Biomedicine of IHM,Division of Life Sciences and Medicine,University of Science&Technology of China,Hefei 230027,China [2]Anhui Key Laboratory for Cellular Dynamics and Chemical Biology,University of Science&Technology of China,Hefei 230027,China [3]Keck Center for Organoids Plasticity,Morehouse School of Medicine,Atlanta,GA 30310,USA [4]Hunan Key Laboratory of Molecular Precision Medicine,Central South University,Changsha 410083,China

出　　处：《Journal of Molecular Cell Biology》2024年第2期24-35,共12页分子细胞生物学报（英文版）

基　　金：supported by grants from the National Key Research and Development Program of China(2022YFA1303100,2022YFA0806800,2022YFA1302700,and 2017YFA0503600);the National Natural Science Foundation of China(32090040,92153302,92254302,92253305,31621002,21922706,92059102,and 92253301);the Plans for Major Provincial Science&Technology Projects of Anhui Province(202303a0702003),the Ministry of Education(IRT_17R102);the Fundamental Research Funds for the Central Universities(KB9100000007 and KB9100000013).

摘　　要：In eukaryotes,microtubule polymers are essential for cellular plasticity and fate decisions.End-binding(EB)proteins serve as scaffolds for orchestrating microtubule polymer dynamics and are essential for cellular dynamics and chromosome segregation in mitosis.Here,we show that EB1 forms molecular condensates with TIP150 and MCAK through liquid–liquid phase separation to compartmentalize the kinetochore–microtubule plus-end machinery,ensuring accurate kinetochore–microtubule interactions during chromosome segregation in mitosis.Perturbation of EB1–TIP150 polymer formation by a competing peptide prevents phase separation of the EB1-mediated complex and chromosome alignment at the metaphase equator in both cultured cells and Drosophila embryos.Lys220 of EB1 is dynamically acetylated by p300/CBP-associated factor in early mitosis,and persistent acetylation at Lys220 attenuates phase separation of the EB1-mediated complex,dissolves droplets in vitro,and harnesses accurate chromosome segregation.Our data suggest a novel framework for understanding the organization and regulation of eukaryotic spindle for accurate chromosome segregation in mitosis.

关 键 词：phase separation MITOSIS microtubule dynamics EB1 ACETYLATION 

分 类 号：Q253[生物学—细胞生物学]