Mitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly

Xu Liu; Leilei Xu; Junying Li; Phil Y.Yao; Wanjuan Wang; Hazrat Ismail; Haowei Wang; Bryce Liao; Zhihong Yang; Tarsha Ward; Ke Ruan; Jianchun Zhang; Quan Wu; Ping He; Xia Ding; Dongmei Wang; Chuanhai Fu; Zhen Dou; Feng Yan; Wenwen Wang; Xing Liu; Xuebiao Yao

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Mitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly

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Error-free cell division depends on the accurate assembly of the spindle midzone from dynamic spindle microtubules to ensure chromatid segregation during metaphase-anaphase transition.However,the mechanism underlying the key transition from the mitotic spindle to central spindle before anaphase onset remains elusive.Given the prevalence of chromosome instability phenotype in gastric tumorigenesis,we developed a strategy to model context-dependent cell division using a combination of light sheet microscope and 3D gastric organoids.Light sheet microscopic image analyses of 3D organoids showed that CENP-E inhibited cells undergoing aberrant metaphase-anaphase transition and exhibiting chromosome segregation errors during mitosis.Highresolution real-time imaging analyses of 2D cell culture revealed that CENP-E inhibited cells undergoing central spindle splitting and chromosome instability phenotype.Using biotinylated syntelin as an affinity matrix,we found that CENP-E forms a complex with PRC1 in mitotic cells.Chemical inhibition of CENP-E in metaphase by syntelin prevented accurate central spindle assembly by perturbing temporal assembly of PRC1 to the midzone.Thus,CENP-E-mediated PRC1 assembly to the central spindle constitutes a temporal switch to organize dynamic kinetochore microtubules into stable midzone arrays.These findings reveal a previously uncharacterized role of CENP-E in temporal control of central spindle assembly.Since CENP-E is absent from yeast,we reasoned that metazoans evolved an elaborate central spindle organization machinery to ensure accurate sister chromatid segregation during anaphase and cytokinesis.

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《分子细胞生物学报：英文版》 |2020年第8期|654-665|共12页
作者
Xu Liu; Leilei Xu; Junying Li; Phil Y.Yao; Wanjuan Wang; Hazrat Ismail; Haowei Wang; Bryce Liao; Zhihong Yang; Tarsha Ward; Ke Ruan; Jianchun Zhang; Quan Wu; Ping He; Xia Ding; Dongmei Wang; Chuanhai Fu; Zhen Dou; Feng Yan; Wenwen Wang; Xing Liu; Xuebiao Yao;
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作者单位

MOE Key Laboratory for Cellular Dynamics&Anhui Key Laboratory for Chemical Biology;

CAS Center for Excellence in Molecular Cell Science;

Hefei National Science Center for Physical Sciences at Microscale&University of Science and Technology of China;

Hefei 230027;

China;

Department of Physiology;

Morehouse School of Medicine;

Atlanta;

GA 30310;

USA;

School of Basic Medical Sciences;

Beijing University of Chinese Medicine;

Beijing 100029;

China;

Department of Biology;

Duke University Durham;

NC 27708;

USA;

Institute of ProteoGenomics;

Beijing 100029;

China;

Harvard Medical School;

Boston;

MA 02115;

USA;

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原文格式 PDF
正文语种 chi
中图分类遗传学分支学科;
关键词
organoids.cell division; central spindle; CENP-E; syntelin; PRC1;

Mitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly

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