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Mitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly
Xu Liu1,2,† , Leilei Xu1,† , Junying Li1 , Phil Y. Yao2 , Wanjuan Wang1,3 , Hazrat Ismail1 , Haowei Wang1 , Bryce Liao2,4 , Zhihong Yang5 , Tarsha Ward2,6 , Ke Ruan1 , Jianchun Zhang1 , Quan Wu1 , Ping He1 , Xia Ding1,3 , Dongmei Wang1,2 , Chuanhai Fu1 , Zhen Dou1,2 , Feng Yan1 , Wenwen Wang1,2,* , Xing Liu1,2,* , Xuebiao Yao1
1MOE 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
2Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA
3School of Basic Medical Sciences, Beijing University of Chinese Medicine, Beijing 100029, China
4Department of Biology, Duke University Durham, NC 27708, USA
5Institute of ProteoGenomics, Beijing 100029, China
6Harvard Medical School, Boston, MA 02115, USA
These authors contributed equally to this work
*Correspondence to:Wenwen Wang , Email:wwwang@ustc.edu.cn Xing Liu , Email:xing1017@ustc.edu.cn
J Mol Cell Biol, Volume 12, Issue 8, August 2020, Pages 654-665  https://doi.org/10.1093/jmcb/mjz051
Keyword: organoids, cell division, central spindle, CENP-E, syntelin, PRC1

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. High-resolution 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.