Journal of Molecular Cell Biology最新文献

{"title":"In vitro oogenesis and parthenogenetic development of chicken female germ cells.","authors":"Yuxiao Ma, Changhao Yu, Jiahui Wei, Feiyi Wang, Qing Sun, Jingui Hao, Zimo Zhu, Pengxiang Zhao, Guiyu Zhu","doi":"10.1093/jmcb/mjag013","DOIUrl":"https://doi.org/10.1093/jmcb/mjag013","url":null,"abstract":"<p><p>In vitro reconstruction of gametogenesis is an important research direction in germ cell biology and assisted reproduction. While substantial progress has been made in the in vitro oogenesis of mammalian germ cells, analogous approaches in avian species remain unexplored. In this study, we investigated the capacity of chicken primordial germ cells (PGCs) and oogonial stem cells (OSCs) to differentiate into oocyte-like cells in vitro. Under meiotic induction with retinoic acid and vitamin C, both PGCs and OSCs initiated meiosis but arrested at the prophase I stage. Subsequent exposure to follicle-stimulating hormone, human chorionic gonadotropin, and progesterone facilitated the resumption of meiosis, leading to the formation of secondary oocytes. Next, parthenogenetic activation experiments showed that these germ cell-derived secondary oocytes were capable of undergoing cleavage and developing into blastomeres. Furthermore, in the aged and stopped-laying ovaries, OSCs retained the proliferation ability but lost their differentiation potential to increase the risk of germ cell tumor. The current in vitro oogenesis system enabled evaluation of healthy and compromised oocytes in avian species. This study not only provides direct evidence for the in vitro recapitulation of oogenesis in birds but also offers new avenues for preserving female germ cells and mass production of chicken oocytes.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486342","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}

{"title":"A high-throughput method for quantifying relative telomere length in single cells in situ combined with live-cell imaging.","authors":"Qingyang Sun, Zhengzhi Zou, Mingwei Min","doi":"10.1093/jmcb/mjaf046","DOIUrl":"10.1093/jmcb/mjaf046","url":null,"abstract":"","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13000372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634825","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}

{"title":"T-cadherin deprivation in endothelial cells promotes vascular injury in Kawasaki disease through SOD2/ROS/NLRP3 pathway-mediated pyroptosis.","authors":"Yueling Lin, Fei Wang, Xilian Luo, Xiangna Yang, Wan Yang, Zhaojin Lu, Zhouping Wang, Huazhong Zhou, Meiying Ruan, Kaining Chen, Lanyan Fu, Lei Pi, Di Che, Hongyan Yu, Xiaoqiong Gu","doi":"10.1093/jmcb/mjaf039","DOIUrl":"10.1093/jmcb/mjaf039","url":null,"abstract":"<p><p>Kawasaki disease (KD) is an acute febrile systemic vasculitis associated with the development of coronary artery lesion and coronary artery aneurysm. This condition is characterized by sustained vascular inflammation and endothelial dysfunction, in which pyroptosis serves as a pivotal driver of inflammatory response. However, the molecular mechanisms linking pyroptosis to endothelium injury and KD pathogenesis remain poorly understood. Analysis of public datasets revealed a marked decrease in T-cadherin (T-cad, CDH13) expression in cardiac tissues from KD patients and KD model mice compared to controls. In vitro and in vivo experiments revealed the reduced T-cad expression in both the treated human umbilical vein endothelial cells (HUVECs) and the abdominal aorta of Lactobacillus casei cell wall extract-induced KD mice. RNA sequencing analysis of HUVECs with siRNA-mediated T-cad knockdown showed significant enrichment of genes involved in pro-inflammatory cascades and pyroptosis-associated pathways. Western blot analysis further validated the upregulation of pyroptosis-associated proteins, including NLRP3, caspase-1, GSDMD, IL-1β, and IL-18, in the T-cad knockdown group compared to controls. These findings were supported by functional assays demonstrating the increased lactate dehydrogenase release, higher TUNEL-positive cells, and elevated reactive oxygen species (ROS) levels in the T-cad knockdown group. Collectively, our results indicate that inflammatory stimuli downregulate T-cad expression in endothelial cells, subsequently reducing superoxide dismutase 2 (SOD2) expression and its enzymatic activity. This leads to ROS accumulation, which activates the NLRP3 inflammasome and initiates pyroptosis. Thus, T-cad deficiency induces pyroptosis in HUVECs via the activation of the SOD2/ROS/NLRP3 pathway. These findings highlight the pivotal role of T-cad deprivation-mediated endothelial cell pyroptosis in the initiation and progression of KD, providing novel insights into its pathophysiology and potential therapeutic targets.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145489077","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}

{"title":"BAR-PH tandem of ACAP4 remodels membranes to drive migration via Ezrin-dependent activation.","authors":"Shan Huang, Jiasheng Chen, Xinyu Wang, Xiaoyu Song, Xiaojie Zhu, Chuanhai Fu, Xuan Zhang, Xing Liu, Chao Wang","doi":"10.1093/jmcb/mjaf038","DOIUrl":"10.1093/jmcb/mjaf038","url":null,"abstract":"<p><p>ADP-ribosylation factor (Arf)-specific GTPase-activating proteins (ArfGAPs) regulate cell migration through interactions with small G proteins, including Arfs. In ArfGAPs, the Bin/Amphiphysin/Rvs (BAR) domain plays a key role in membrane binding and curvature induction, yet the molecular mechanisms underlying these processes remain unclear. Here, we investigate the function of the BAR domain and its adjacent pleckstrin homology (PH) domain of ACAP4 in cell migration. We demonstrate that the BAR-PH tandem of ACAP4 induces membrane curvature, promotes cell migration, forms condensates in vitro, and exhibits membrane-associated distribution in cells. The crystal structure of the ACAP4 BAR domain, determined at 2.8 Å resolution, reveals multiple positively charged surface patches. Structural modeling further identifies conserved positively charged residue pairs in the PH domain, which collectively mediate electrostatic interactions essential for both membrane remodeling and membrane localization. Mutagenesis experiments confirm that these regions are required for ACAP4's subcellular localization and pro-migratory activity. Furthermore, we identify that the actin-binding protein Ezrin interacts with a specific C-terminal region of ACAP4 to regulate its function. Ezrin binding enhances condensate formation and enables full-length ACAP4 to associate with membranes and promote cell migration, particularly when co-expressed with the activated Ezrin (T567D). Together, our findings uncover the molecular basis by which ACAP4 coordinates membrane remodeling and cytoskeletal dynamics, offering new insights into the mechanisms that drive cell migration.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13000378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444984","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}

{"title":"The tumor-associated fibroblasts regulate urothelial carcinoma progression.","authors":"Yu Xiao, Junfeng Yang, Mengjie Sun, Yongfu Li, Qinyin Liu, Jinjun Leng, Maolin Yang, Jinrui Wang, Hongju Li, Caifeng Yang, Changfen Luo, Jiahong Li, Longli Kang, Fen Huang, Yanhong Yu, Chuanmao Zhang","doi":"10.1093/jmcb/mjaf032","DOIUrl":"10.1093/jmcb/mjaf032","url":null,"abstract":"<p><p>Tumor-associated fibroblasts (CAFs) regulate tumorigenesis, tumor cell proliferation, and metastasis via secreting related regulatory factors; however, the role of CAFs in regulating the development of upper tract urothelial carcinoma (UTUC) remains unclear. Here, by utilizing single-cell RNA sequencing, single-nucleus RNA sequencing, SpaTial enhanced resolution omics-sequencing, and UTUC immunofluorescence chip cohort to construct the first comprehensive microenvironmental atlas of CAFs, we investigated the roles of CAFs in UTUC progression. Through hierarchical clustering and the copy number variation scores of UTUC epithelial cells, we classified tumor epithelial cells into high-malignant, medium-malignant, and low-malignant potential categories. We found pronounced interaction signals between different CAF subclusters and all three types of epithelial cells, among which high-malignant epithelial cells exhibited the most significant communication signals with the myofibroblastic CAFs1 (myCAFs1) and myCAFs2 subclusters, and FN1 and COL1A1 generated by CAFs played critical roles in this process, suggesting that the progression of UTUC may be attributed to the activation of tumor cells by CAFs. Additionally, both myCAFs1 and myCAFs2 simultaneously affect bladder urothelial carcinoma (BUC) prognosis, with the risk model showing good consistency across cohorts. Therefore, this study constructs a multi-omics landscape of UTUC and identifies common prognostic markers shared with BUC.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13032880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091953","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}

{"title":"Zbtb38 transcriptionally activates XIAP to regulate apoptosis in development and cancer.","authors":"Toshiaki Shigeoka, Hiroyuki Nagaoka, Nunuk Aries Nurulita, Shogo Tada, Yasumasa Bessho, Yasumasa Ishida, Eishou Matsuda","doi":"10.1093/jmcb/mjag011","DOIUrl":"https://doi.org/10.1093/jmcb/mjag011","url":null,"abstract":"<p><p>The X-linked inhibitor of apoptosis protein (XIAP) is a key suppressor of apoptosis, crucial for cellular differentiation, embryogenesis, and cancer progression. However, its upstream regulatory mechanisms remain poorly understood. Here, we demonstrate that the zinc finger transcription factor Zbtb38, a negative regulator of apoptosis, modulates XIAP expression in both loss- and gain-of-function experiments, irrespective of p53 expression. Notably, XIAP overexpression rescues the apoptosis induced by Zbtb38 knockdown, indicating that Zbtb38-associated apoptosis is at least partially XIAP-dependent. Mechanistically, Zbtb38 binds to E-box motifs within upstream regulatory regions of XIAP and activates its transcription. During embryonic stem cell differentiation and embryogenesis, Zbtb38 depletion increases apoptosis and reduces XIAP and Bcl-2 expression, underscoring their functional relevance in these processes. Analysis of human tumor datasets reveals a strong positive correlation between ZBTB38 and XIAP expression, with elevated ZBTB38 levels associated with high-grade malignancies. Furthermore, Zbtb38 knockdown induces apoptosis in cancer cells with reduced XIAP expression, regardless of p53 expression. Collectively, these findings uncover a novel Zbtb38-XIAP axis that regulates apoptosis during cellular differentiation, development, and oncogenesis and highlight its therapeutic potential in XIAP-driven and p53-deficient tumors.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473881","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}

{"title":"Transcriptional co-activators YAP/TAZ in cancer-associated fibroblasts are dispensable for Notch-driven intrahepatic cholangiocarcinoma.","authors":"Tingting Deng, Yuemei Qiao, Xinyu Xie, Yanjun Wu, Gaoxiang Ge","doi":"10.1093/jmcb/mjag010","DOIUrl":"https://doi.org/10.1093/jmcb/mjag010","url":null,"abstract":"","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468265","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}

{"title":"Amphioxus tyrosine kinase SYK inhibits NF-κB activation through MyD88-dependent mechanism.","authors":"Jie Xu, Haikun Hu, Qingyi Lu, Qiuzhu Wei, Yuhang Zhang, Guangrui Huang, Anlong Xu","doi":"10.1093/jmcb/mjag009","DOIUrl":"https://doi.org/10.1093/jmcb/mjag009","url":null,"abstract":"<p><p>The spleen tyrosine kinase (SYK) plays pivotal roles in the adaptive immune response by recognizing phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) and activating downstream effectors. However, the emergence of SYK predates the advent of adaptive immunity, and its original functions independent of the adaptive immune system remain largely unknown. In this study, we identified and characterized a SYK homolog (bjSYK) in the amphioxus Branchiostoma japonicum, a key model for understanding immune system evolution. Phylogenetic analysis positioned bjSYK basally among deuterostome SYK kinases. Expression analysis revealed its localization in immune-relevant tissues. Contrary to the canonical activating role in vertebrates, functional studies demonstrated that bjSYK acts as a potent suppressor of NF-κB activation. Specifically, bjSYK directly interacts with bjMyD88 via its SH2 domains binding to a conserved hemi-ITAM motif, suppressing K63-linked polyubiquitination of bjMyD88 and consequently inhibiting bjMyD88-dependent NF-κB signaling. Furthermore, bjSYK also suppresses NF-κB activation through bjTRAF6, a key adaptor downstream of bjMyD88, by inhibiting its ubiquitination. These findings reveal an evolutionarily ancient inhibitory role of bjSYK in NF-κB signaling in basal chordate innate immunity, suggesting that SYK-mediated negative regulation of Toll-like receptor pathways originates in amphioxus and provides a foundation for the context-dependent functions of SYK in vertebrate immunity.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468231","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}

{"title":"Preserving the UFMylation-cilium axis mitigates blue light-induced retinal degeneration.","authors":"Guizhi Guo, Runa Wang, Sai Zhang, Yufei Zhang, Lin Li, Miaoyuan Liu, Long Yin, Changfeng Wei, Yingxin Gong, Li Jiao, Dengwen Li, Jun Zhou, Min Liu, Jie Ran","doi":"10.1093/jmcb/mjag007","DOIUrl":"https://doi.org/10.1093/jmcb/mjag007","url":null,"abstract":"<p><p>Blue light damage (BLD) is a complex process implicated in a variety of ocular diseases, including age-related macular degeneration and dry eye diseases. However, the molecular mechanisms underlying the BLD process remain largely unknown. In this study, using a mouse model, we identify photoreceptor cilium disruption as a key event in BLD and show that the UFMylation of kinesin family member 11 (KIF11) is decreased under BLD conditions. We further reveal that ubiquitin-fold modifier 1-specific ligase 1 (UFL1), the sole ligase for UFMylation, localizes to the basal body and is required for maintaining photoreceptor cilia. Strikingly, exposure to blue light disrupts the basal body localization of UFL1, leading to ciliary defects and subsequent photoreceptor dysfunction. Ufl1 knockout mice exhibit similar ciliary donlefects and retinal impairments. Importantly, intravitreal injection of agents that enhance UFMylation or ciliogenesis can mitigate the pathological changes induced by blue light exposure. These findings establish that UFL1-mediated ciliary integrity contributes to retinal deficits associated with BLD and demonstrate that targeting the UFMylation-cilium axis represents a promising therapeutic strategy for BLD-associated retinal diseases.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444078","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}

{"title":"Methylation of MATCAP by PRMT5 regulates microtubule detyrosination to ensure mitotic fidelity.","authors":"Tongtong Yang, Wenping Hu, Yaqian Zhang, Fangyuan Xiong, Zhikai Wang, Xing Liu, Kai Jiang, Xuebiao Yao, Liangyu Zhang","doi":"10.1093/jmcb/mjag008","DOIUrl":"https://doi.org/10.1093/jmcb/mjag008","url":null,"abstract":"<p><p>During mitosis, motor protein-driven chromosome motility is essential for faithful chromosome segregation. The tubulin code, comprising tubulin isotypes and post-translational modifications, guides motor proteins along microtubules. Recent studies show that MATCAP-mediated α-tubulin detyrosination guides proper chromosome congression and segregation during mitosis. However, the mechanisms of action underlying MATCAP activity regulation remain poorly understood. Here, we identify PRMT5 as a novel MATCAP methyl-transferase and that the methylation guides MATCAP activity for chromosome alignment. PRMT5 depletion or inhibition impairs chromosome alignment and segregation. Biochemical analyses reveal that MATCAP interacts with PRMT5 and is a bona fide substrate of PRMT5. Our mass spectrometry analyses show that PRMT5 symmetrically dimethylates the N-terminus of MATCAP at Arg74, Arg99, and Arg104. Importantly, the PRMT5-elicited methylation attenuates MATCAP's microtubule-binding and detyrosination activities. Loss of PRMT5 or expression of non-methylatable MATCAP mutants causes excessive tubulin detyrosination and disrupts chromosome congression. These findings suggest that PRMT5-mediated dynamic methylation of MATCAP is a novel regulatory mechanism that guides accurate tyrosination and ensures mitotic fidelity.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433796","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}