Journal of Molecular Cell Biology最新文献_第2页

Aurora B promotes the CENP-T-CENP-W interaction to guide accurate chromosome segregation in mitosis. 极光 B 促进 CENP-T-CENP-W 相互作用，引导有丝分裂中染色体的准确分离。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-29 DOI: 10.1093/jmcb/mjae001

Wei Liu, Zhen Dou, Chunyue Wang, Gangyin Zhao, Fengge Wu, Chunli Wang, Felix Aikhionbare, Mingliang Ye, Divine Mensah Sedzro, Zhenye Yang, Chuanhai Fu, Zhikai Wang, Xinjiao Gao, Xuebiao Yao, Xiaoyu Song, Xing Liu

{"title":"Aurora B promotes the CENP-T-CENP-W interaction to guide accurate chromosome segregation in mitosis.","authors":"Wei Liu, Zhen Dou, Chunyue Wang, Gangyin Zhao, Fengge Wu, Chunli Wang, Felix Aikhionbare, Mingliang Ye, Divine Mensah Sedzro, Zhenye Yang, Chuanhai Fu, Zhikai Wang, Xinjiao Gao, Xuebiao Yao, Xiaoyu Song, Xing Liu","doi":"10.1093/jmcb/mjae001","DOIUrl":"10.1093/jmcb/mjae001","url":null,"abstract":"Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules. Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network (CCAN) during chromosome segregation. CCAN contains 16 subunits, including CENP-W and CENP-T. However, the molecular recognition and mitotic regulation of the CCAN assembly remain elusive. Here, we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T. Aurora B phosphorylates CENP-W at threonine 60, which enhances the interaction between CENP-W and CENP-T to ensure robust metaphase chromosome alignment and accurate chromosome segregation in mitosis. These findings delineate a conserved signaling cascade that integrates protein phosphorylation with CCAN integrity for the maintenance of genomic stability.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PLK1 phosphorylation of ZW10 guides accurate chromosome segregation in mitosis. ZW10的PLK1磷酸化可引导有丝分裂中染色体的准确分离。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-29 DOI: 10.1093/jmcb/mjae008

Sm Faysal Bellah, Fangyuan Xiong, Zhen Dou, Fengrui Yang, Xing Liu, Xuebiao Yao, Xinjiao Gao, Liangyu Zhang

{"title":"PLK1 phosphorylation of ZW10 guides accurate chromosome segregation in mitosis.","authors":"Sm Faysal Bellah, Fangyuan Xiong, Zhen Dou, Fengrui Yang, Xing Liu, Xuebiao Yao, Xinjiao Gao, Liangyu Zhang","doi":"10.1093/jmcb/mjae008","DOIUrl":"10.1093/jmcb/mjae008","url":null,"abstract":"Stable transmission of genetic information during cell division requires faithful chromosome segregation. Mounting evidence has demonstrated that polo-like kinase 1 (PLK1) dynamics at kinetochores control correct kinetochore-microtubule attachments and subsequent silencing of the spindle assembly checkpoint. However, the mechanisms underlying PLK1-mediated silencing of the spindle checkpoint remain elusive. Here, we identified a regulatory mechanism by which PLK1-elicited zeste white 10 (ZW10) phosphorylation regulates spindle checkpoint silencing in mitosis. ZW10 is a cognate substrate of PLK1, and the phosphorylation of ZW10 at Ser12 enables dynamic ZW10-Zwint1 interactions. Inhibition of ZW10 phosphorylation resulted in misaligned chromosomes, while persistent expression of phospho-mimicking ZW10 mutant caused premature anaphase, in which sister chromatids entangled as cells entered anaphase. These findings reveal the previously uncharacterized PLK1-ZW10 interaction through which dynamic phosphorylation of ZW10 fine-tunes accurate chromosome segregation in mitosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11328731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CSPP1 stabilizes microtubules by capping both plus and minus ends. CSPP1 通过封盖正负两端来稳定微管。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-29 DOI: 10.1093/jmcb/mjae007

Zhikai Wang, Wenwen Wang, Shuaiyu Liu, Fengrui Yang, Xu Liu, Shasha Hua, Lijuan Zhu, Aoqing Xu, Donald L Hill, Dongmei Wang, Kai Jiang, Jennifer Lippincott-Schwartz, Xing Liu, Xuebiao Yao

{"title":"CSPP1 stabilizes microtubules by capping both plus and minus ends.","authors":"Zhikai Wang, Wenwen Wang, Shuaiyu Liu, Fengrui Yang, Xu Liu, Shasha Hua, Lijuan Zhu, Aoqing Xu, Donald L Hill, Dongmei Wang, Kai Jiang, Jennifer Lippincott-Schwartz, Xing Liu, Xuebiao Yao","doi":"10.1093/jmcb/mjae007","DOIUrl":"10.1093/jmcb/mjae007","url":null,"abstract":"Although the dynamic instability of microtubules (MTs) is fundamental to many cellular functions, quiescent MTs with unattached free distal ends are commonly present and play important roles in various events to power cellular dynamics. However, how these free MT tips are stabilized remains poorly understood. Here, we report that centrosome and spindle pole protein 1 (CSPP1) caps and stabilizes both plus and minus ends of static MTs. Real-time imaging of laser-ablated MTs in live cells showed deposition of CSPP1 at the newly generated MT ends, whose dynamic instability was concomitantly suppressed. Consistently, MT ends in CSPP1-overexpressing cells were hyper-stabilized, while those in CSPP1-depleted cells were much more dynamic. This CSPP1-elicited stabilization of MTs was demonstrated to be achieved by suppressing intrinsic MT catastrophe and restricting polymerization. Importantly, CSPP1-bound MTs were resistant to mitotic centromere-associated kinesin-mediated depolymerization. These findings delineate a previously uncharacterized CSPP1 activity that integrates MT end capping to orchestrate quiescent MTs.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Organization of microtubule plus-end dynamics by phase separation in mitosis. 通过有丝分裂中的相分离组织微管加端动力学

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-29 DOI: 10.1093/jmcb/mjae006

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

{"title":"Organization of microtubule plus-end dynamics by phase separation in mitosis.","authors":"Fengrui Yang, Mingrui Ding, Xiaoyu Song, Fang Chen, Tongtong Yang, Chunyue Wang, Chengcheng Hu, Qing Hu, Yihan Yao, Shihao Du, Phil Y Yao, Peng Xia, Gregory Adams, Chuanhai Fu, Shengqi Xiang, Dan Liu, Zhikai Wang, Kai Yuan, Xing Liu","doi":"10.1093/jmcb/mjae006","DOIUrl":"10.1093/jmcb/mjae006","url":null,"abstract":"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.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-cell landscape of alternative polyadenylation in human lymphoid hematopoiesis. 人类淋巴造血过程中替代多腺苷酸化的单细胞图谱。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-09 DOI: 10.1093/jmcb/mjae027

Jiaqi Qiang, Shan Yu, Jun Li, Yu Rong, Xiaoshuang Wang, Yong Zhu, Fang Wang

{"title":"Single-cell landscape of alternative polyadenylation in human lymphoid hematopoiesis.","authors":"Jiaqi Qiang, Shan Yu, Jun Li, Yu Rong, Xiaoshuang Wang, Yong Zhu, Fang Wang","doi":"10.1093/jmcb/mjae027","DOIUrl":"https://doi.org/10.1093/jmcb/mjae027","url":null,"abstract":"Alternative polyadenylation (APA) is an essential post-transcriptional process that produces mature mRNA isoforms by regulating the usage of polyadenylation sites (PASs). APA is involved in lymphocyte activation; however, its role throughout the entire differentiation trajectory remains elusive. Here, we analyzed single-cell 3'-end transcriptome data from healthy subjects to construct a dynamic-APA landscape from hematopoietic stem and progenitor cells (HSPCs) to terminally differentiated lymphocytes. This analysis covered 19973 cells of 12 clusters from five lineages (B cells, CD4+ T cells, CD8+ T cells, natural killer cells, and plasmacytoid dendritic cells). A total of 2364 genes exhibited differential 3'UTR PAS usage, and 3021 genes displayed differential intronic cleavage during lymphoid differentiation. We observed a global trend of 3'UTR shortening during lymphoid differentiation. Nevertheless, specific events of both 3'UTR shortening and lengthening were also identified within each cluster. The APA patterns delineated three differentiation stages: HSPCs, precursor cells, and mature cells. Moreover, we demonstrated that the conversion of naïve T cells to memory T cells was accompanied by dynamic APA in transcription factor-encoding genes (TCF7 and NFATC2IP), immune function-related genes (BCL2, CD5, CD28, GOLT1B, and TMEM59), and protein ubiquitination-related genes (UBE2G1, YPEL5, and SUMO3). These findings expand our understanding of the underlying molecular mechanisms of APA and facilitate studies on the regulatory role of APA in lymphoid hematopoiesis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inducible RNA targeting and N6-methyladenosine editing by a split-Cas13 architecture. 分裂 Cas13 架构的诱导性 RNA 靶向和 N6-甲基腺苷编辑。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1093/jmcb/mjae002

Yang Li, Qiang Sun, Zhi Yang, Gang Yuan

引用次数: 0

The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development. TRAF7 螺旋线圈三聚体的结构有助于深入了解其在斑马鱼胚胎发育过程中的功能。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1093/jmcb/mjad083

Xiaozhen Song, Ruixing Hu, Yi Chen, Man Xiao, Hong Zhang, Shengnan Wu, Qing Lu

{"title":"The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development.","authors":"Xiaozhen Song, Ruixing Hu, Yi Chen, Man Xiao, Hong Zhang, Shengnan Wu, Qing Lu","doi":"10.1093/jmcb/mjad083","DOIUrl":"10.1093/jmcb/mjad083","url":null,"abstract":"TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways, contributing to immune responses, tumor progression, and embryonic development. Somatic mutations within the coiled-coil (CC) domain and WD40 repeat domain of TRAF7 could cause brain tumors, while germline pathogenic mutations contribute to severe developmental abnormalities. However, the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains unclear. In this study, we employed zebrafish as an in vivo model system. TRAF7 knock down caused defects in zebrafish embryonic development. We determined the crystal structure of TRAF7 CC domain at 3.3 Å resolution and found that the CC region trimerization was essential for TRAF7 functionality during zebrafish embryonic development. Additionally, disease-causing mutations in TRAF7 CC region could impair the trimer formation, consequently impacting early embryonic development of zebrafish. Therefore, our study sheds light on the molecular mechanism of TRAF7 CC trimer formation and its pivotal role in embryonic development.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rbfox1 controls alternative splicing of focal adhesion genes in cardiac muscle cells. Rbfox1 控制着心肌细胞中局灶粘附基因的替代剪接。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1093/jmcb/mjae003

Peter Zorn, Jaime Calvo Sánchez, Tala Alakhras, Barbara Schreier, Michael Gekle, Stefan Hüttelmaier, Marcel Köhn

{"title":"Rbfox1 controls alternative splicing of focal adhesion genes in cardiac muscle cells.","authors":"Peter Zorn, Jaime Calvo Sánchez, Tala Alakhras, Barbara Schreier, Michael Gekle, Stefan Hüttelmaier, Marcel Köhn","doi":"10.1093/jmcb/mjae003","DOIUrl":"10.1093/jmcb/mjae003","url":null,"abstract":"Alternative splicing is one of the major cellular processes that determine the tissue-specific expression of protein variants. However, it remains challenging to identify physiologically relevant and tissue-selective proteins that are generated by alternative splicing. Hence, we investigated the target spectrum of the splicing factor Rbfox1 in the cardiac muscle context in more detail. By using a combination of in silico target prediction and in-cell validation, we identified several focal adhesion proteins as alternative splicing targets of Rbfox1. We focused on the alternative splicing patterns of vinculin (metavinculin isoform) and paxillin (extended paxillin isoform) and identified both as potential Rbfox1 targets. Minigene analyses suggested that both isoforms are promoted by Rbfox1 due to binding in the introns. Focal adhesions play an important role in the cardiac muscle context, since they mainly influence cell shape, cytoskeletal organization, and cell-matrix association. Our data confirmed that depletion of Rbfox1 changed cardiomyoblast morphology, cytoskeletal organization, and multinuclearity after differentiation, which might be due to changes in alternative splicing of focal adhesion proteins. Hence, our results indicate that Rbfox1 promotes alternative splicing of focal adhesion genes in cardiac muscle cells, which might contribute to heart disease progression, where downregulation of Rbfox1 is frequently observed.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms. 病理相关醛糖和环境醛通过甲酰基介导的机制引起纤毛的破坏。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1093/jmcb/mjad079

Te Li, Min Liu, Fan Yu, Song Yang, Weiwen Bu, Kai Liu, Jia Yang, Hua Ni, Mulin Yang, Hanxiao Yin, Renjie Hong, Dengwen Li, Huijie Zhao, Jun Zhou

{"title":"Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms.","authors":"Te Li, Min Liu, Fan Yu, Song Yang, Weiwen Bu, Kai Liu, Jia Yang, Hua Ni, Mulin Yang, Hanxiao Yin, Renjie Hong, Dengwen Li, Huijie Zhao, Jun Zhou","doi":"10.1093/jmcb/mjad079","DOIUrl":"10.1093/jmcb/mjad079","url":null,"abstract":"Carbohydrate metabolism disorders (CMDs), such as diabetes, galactosemia, and mannosidosis, cause ciliopathy-like multiorgan defects. However, the mechanistic link of cilia to CMD complications is still poorly understood. Herein, we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar alcohols. Moreover, environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl groups. Mechanistic studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane, which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium disassembly. In vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm flagella. These findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The next decade of SET: from an oncoprotein to beyond. SET 的下一个十年：从肿瘤蛋白到超越。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1093/jmcb/mjad082

Han Yao, Meng Zhang, Donglai Wang

引用次数: 0