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| 1 | Mitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly显示文摘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. | 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 | 2020 | Journal of Molecular Cell Biology2020，12，8： | 3 |
| 2 | Acetylation of ezrin regulates membrane–cytoskeleton interaction underlying CCL18-elicited cell migration显示文摘Ezrin,a membrane–cytoskeleton linker protein,plays an essential role in cell polarity establishment,cell migration,and division.Recent studies show that ezrin phosphorylation regulates breast cancer metastasis by promoting cancer cell survivor and promotes intrahepatic metastasis via cell migration.However,it was less characterized whether there are additional post-translational modifications and/or post-translational crosstalks on ezrin underlying context-dependent breast cancer cell migration and invasion.Here we show that ezrin is acetylated by p300/CBP-associated factor(PCAF)in breast cancer cells in response to CCL18 stimulation.Ezrin physically interacts with PCAF and is a cognate substrate of PCAF.The acetylation site of ezrin was mapped by mass spectrometric analyses,and dynamic acetylation of ezrin is essential for CCL18-induced breast cancer cell migration and invasion.Mechanistically,the acetylation reduced the lipid-binding activity of ezrin to ensure a robust and dynamic cycling between the plasma membrane and cytosol in response to CCL18 stimulation.Biochemical analyses show that ezrin acetylation prevents the phosphorylation of Thr567.Using atomic force microscopic measurements,our study revealed that acetylation of ezrin induced its unfolding into a dominant structure,which prevents ezrin phosphorylation at Thr567.Thus,these results present a previously undefined mechanism by which CCL18-elicited crosstalks between the acetylation and phosphorylation on ezrin control breast cancer cell migration and invasion.This suggests that targeting PCAF signaling could be a potential therapeutic strategy for combating hyperactive ezrin-driven cancer progression. | Xiaoyu Song Wanjuan Wang Haowei Wang Xiao Yuan Fengrui Yang Lingli Zhao McKay Mullen Shihao Du Najdat Zohbi Saravanakumar Muthusamy Yalei Cao Jiying Jiang Peng Xia Ping He Mingrui Ding Nerimah Emmett Mingming Ma Quan Wu Hadiyah-Nicole Green Xia Ding Dongmei Wang Fengsong Wang Xing Liu | 2020 | Journal of Molecular Cell Biology2020，12，6： | 1 |
| 3 | The septin complex links the catenin complex to the actin cytoskeleton for establishing epithelial cell polarity显示文摘Cell polarity is essential for spatially regulating of physiological processes in metazoans by which hormonal stimulation‒secretion coupling is precisely coupled for tissue homeostasis and organ communications.However,the molecular mechanisms underlying epithelial cell polarity establishment remain elusive.Here,we show that septin cytoskeleton interacts with catenin complex to organize a functional domain to separate apical from basal membranes in polarized epithelial cells.Using polarized epithelial cell monolayer as a model system with transepithelial electrical resistance as functional readout,our studies show that septins are essential for epithelial cell polarization.Our proteomic analyses discovered a novel septin‒catenin complex during epithelial cell polarization.The functional relevance of septin‒catenin complex was then examined in three-dimensional(3D)culture in which suppression of septins resulted in deformation of apical lumen in cysts,a hallmark seen in polarity-deficient 3D cultures and animals.Mechanistically,septin cytoskeleton stabilizes the association of adherens catenin complex with actin cytoskeleton,and depletion or disruption of septin cytoskeleton liberates adherens junction and polarity complexes into the cytoplasm.Together,these findings reveal a previously unrecognized role for septin cytoskeleton in the polarization of the apical‒basal axis and lumen formation in polarized epithelial cells. | Xueying Wang Wenwen Wang Xiwei Wang Ming Wang Lijuan Zhu Fatima Garba Chuanhai Fu Barbara Zieger Xu Liu Xing Liu Xuebiao Yao | 2021 | Journal of Molecular Cell Biology2021，13，6： | 1 |
| 4 | Mps1 dimerization and multisite interactions with Ndc80 complex enable responsive spindle assembly checkpoint signaling显示文摘Error-free mitosis depends on accurate chromosome attachment to spindle microtubules,which is monitored by the spindle assembly checkpoint(SAC)signaling.As an upstream factor of SAC,the precise and dynamic kinetochore localization of Mps1 kinase is critical for initiating and silencing SAC signaling.However,the underlying molecular mechanism remains elusive.Here,we demonstrated that the multisite interactions between Mps1 and Ndc80 complex(Ndc80C)govern Mps1 kinetochore targeting.Importantly,we identified direct interaction between Mps1 tetratricopeptide repeat domain and Ndc80C.We further identified that Mps1 C-terminal fragment,which contains the protein kinase domain and C-tail,enhances Mps1 kinetochore localization.Mechanistically,Mps1 C-terminal fragment mediates its dimerization.Perturbation of C-tail attenuates the kinetochore targeting and activity of Mps1,leading to aberrant mitosis due to compromised SAC function.Taken together,our study highlights the importance of Mps1 dimerization and multisite interactions with Ndc80C in enabling responsive SAC signaling. | Ping Gui Divine M.Sedzro Xiao Yuan Sikai Liu Mohan Hei Wei Tian Najdat Zohbi Fangwei Wang Yihan Yao Felix O.Aikhionbare Xinjiao Gao Dongmei Wang Xuebiao Yao Zhen Dou | 2020 | Journal of Molecular Cell Biology2020，12，7： | 1 |
| 5 | Methylation of PLK1 by SET7/9 ensures accurate kinetochore–microtubule dynamics显示文摘Faithful segregation of mitotic chromosomes requires bi-orientation of sister chromatids, which relies on the sensing of correct attachments between spindle microtubules and kinetochores. Although the mechanisms underlying PLK1 activation have been extensively studied, the regulatory mechanisms that couple PLK1 activity to accurate chromosome segregation are not well understood. In particular, PLK1 is implicated in stabilizing kinetochore–microtubule attachments, but how kinetochore PLK1 activity is regulated to avoid hyperstabilized kinetochore–microtubules in mitosis remains elusive. Here, we show that kinetochore PLK1 kinase activity is modulated by SET7/9 via lysine methylation during early mitosis. The SET7/9-elicited dimethylation occurs at the Lys191 of PLK1, which tunes down its activity by limiting ATP utilization. Overexpression of the non-methylatable PLK1 mutant or chemical inhibition of SET7/9 methyltransferase activity resulted in mitotic arrest due to destabilized kinetochore–microtubule attachments. These data suggest that kinetochore PLK1 is essential for stable kinetochore–microtubule attachments and methylation by SET7/9 promotes dynamic kinetochore–microtubule attachments for accurate error correction. Our findings define a novel homeostatic regulation at the kinetochore that integrates protein phosphorylation and methylation with accurate chromosome segregation for maintenance of genomic stability. | Ruoying Yu Huihui Wu Hazrat Ismail Shihao Du Jun Cao Jianyu Wang Tarsha Ward Fengrui Yang Ping Gui Mahboob Ali Lingluo Chu Fei Mo Qi Wang Youjun Chu Jianye Zang Yun Zhao Mingliang Ye Guowei Fang Peng RChen Zhen Dou Xinjiao Gao Wenwen Wang Xing Liu Xuebiao Yao | 2020 | Journal of Molecular Cell Biology2020，12，6： | 0 |
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