Journal of Molecular Cell Biology最新文献_第4页

Cnp1 N-terminal dynamics regulate L1 loop recognition by Mis15 to orchestrate kinetochore assembly in Schizosaccharomyces pombe. 在裂糖酵母中，Cnp1 n端动态调节Mis15对L1环的识别，以协调着丝粒组装。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-03 DOI: 10.1093/jmcb/mjaf056

Yujie Xiong, Yanze Jian, Yongliang Zhang, Min Zhang, Xuan Zhang, Kaiming Zhang, Chuanhai Fu, Tian Tian, Jianye Zang

{"title":"Cnp1 N-terminal dynamics regulate L1 loop recognition by Mis15 to orchestrate kinetochore assembly in Schizosaccharomyces pombe.","authors":"Yujie Xiong, Yanze Jian, Yongliang Zhang, Min Zhang, Xuan Zhang, Kaiming Zhang, Chuanhai Fu, Tian Tian, Jianye Zang","doi":"10.1093/jmcb/mjaf056","DOIUrl":"10.1093/jmcb/mjaf056","url":null,"abstract":"Centromeres are defined by the histone H3 variant CENP-A, which serves as the foundation for kinetochore assembly to ensure faithful chromosome segregation. CENP-A nucleosomes possess distinctive dynamic features, including flexible DNA ends at the entry/exit sites and a mobile N-terminal region, which are properties proposed to facilitate kinetochore assembly, yet the underlying molecular mechanisms remain elusive. Here, we present cryo-electron microscopy structures of Cnp1-the Schizosaccharomyces pombe ortholog of CENP-A-nucleosomes alone and in complex with Mis15, the fission yeast ortholog of CENP-N. By integrating structural, biochemical, and molecular dynamics analyses, we demonstrate that the N-terminal region of Cnp1 regulates both DNA-end breathing and the conformational mobility of the L1 loop, a critical structural element for Mis15 recognition. Either enhanced dynamics caused by N-terminal deletion or reduced dynamics from targeted residue substitution disrupt Mis15 binding in vitro and impair its centromeric localization in vivo, thereby compromising the earliest steps of constitutive centromere-associated network assembly. Our findings establish the Cnp1 N-terminus as a dynamic allosteric modulator of chromatin architecture and reveal an L1 loop modulation mechanism that links nucleosome flexibility to kinetochore specification and chromosome segregation fidelity in fission yeast.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843715","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

Amphioxus tyrosine kinase SYK inhibits NF-κB activation through MyD88-dependent mechanism. 文文鱼酪氨酸激酶SYK通过myd88依赖机制抑制NF-κB活化。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-03 DOI: 10.1093/jmcb/mjag009

Jie Xu, Haikun Hu, Qingyi Lu, Qiuzhu Wei, Yuhang Zhang, Guangrui Huang, Anlong Xu

{"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":"10.1093/jmcb/mjag009","url":null,"abstract":"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 nuclear factor-kappa B (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.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344425/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetically-determined systemic lupus erythematosus requires persistent CAR-T therapy: challenging the transient depletion paradigm. 遗传决定的系统性红斑狼疮需要持续的CAR-T治疗：挑战短暂耗尽范式。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-03 DOI: 10.1093/jmcb/mjag002

Baichuan Liu, Wenchen Ruan, Jingwei Jiang, Jinjiao Wang, Li Li, Xindong Liu, Haopeng Wang

引用次数: 0

Filippi syndrome-associated CKAP2L modulates microtubule dynamics essential for mitosis and ciliary length regulation. Filippi综合征相关的CKAP2L调节微管动力学对有丝分裂和纤毛长度调节至关重要。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-03 DOI: 10.1093/jmcb/mjaf054

Qian Lyu, Yinghao Wang, Jun Zhou, Huijie Zhao, Tao Zhong, Qingchao Li

{"title":"Filippi syndrome-associated CKAP2L modulates microtubule dynamics essential for mitosis and ciliary length regulation.","authors":"Qian Lyu, Yinghao Wang, Jun Zhou, Huijie Zhao, Tao Zhong, Qingchao Li","doi":"10.1093/jmcb/mjaf054","DOIUrl":"10.1093/jmcb/mjaf054","url":null,"abstract":"Mutations in the gene encoding cytoskeleton-associated protein 2-like (CKAP2L) have been identified as a causative factor for Filippi syndrome, a rare developmental disorder characterized by facial dysmorphism, syndactyly, and microcephaly. However, the cellular and molecular mechanisms by which CKAP2L contributes to the pathogenesis of this syndrome remain largely unknown. Here, we generated a Ckap2l knockout mouse model to investigate the in vivo and cellular roles of CKAP2L. Interestingly, Ckap2l knockout mice show no overt developmental abnormalities, with the exception of reduced male fertility, evidenced by decreased sperm count, impaired motility, and abnormally elongated flagella. At the cellular level, CKAP2L is a bona fide microtubule-associated protein that localizes to microtubule-based organelles, including the centrosome, mitotic spindle, and ciliary basal body. Depletion of CKAP2L leads to shortened mitotic spindles and cytokinesis failure, resulting in multinucleation. Furthermore, we uncover a conserved function for CKAP2L as a negative regulator of primary cilium length; its loss markedly increases ciliary length in both human and mouse cells. Collectively, these findings position CKAP2L as a multifunctional regulator of microtubule-based organelles and suggest that Filippi syndrome can be classified as a 'centrosomopathy' arising from concurrent defects in cell proliferation and ciliary function.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13417012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145714658","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

Screening the composition of tubulin isotypes reveals the most abundant TUBB4B for ciliary polarity in ependymal cells. 筛选微管蛋白同型的组成，发现室管膜细胞中最丰富的TUBB4B为纤毛极性。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-03 DOI: 10.1093/jmcb/mjaf057

Yanling Liu, Mingyi Liu, Huaqing Xue, Boran Chang, Fengxia Shao, Suhao Cao, Jinsong Li, Xu Zhang, Lei Diao, Lan Bao

{"title":"Screening the composition of tubulin isotypes reveals the most abundant TUBB4B for ciliary polarity in ependymal cells.","authors":"Yanling Liu, Mingyi Liu, Huaqing Xue, Boran Chang, Fengxia Shao, Suhao Cao, Jinsong Li, Xu Zhang, Lei Diao, Lan Bao","doi":"10.1093/jmcb/mjaf057","DOIUrl":"10.1093/jmcb/mjaf057","url":null,"abstract":"Cilia are microtubule-based organelles that protrude from the surface of various eukaryotic cell types. Microtubules are assembled by α/β-tubulin heterodimers, all of which comprise multiple isotypes encoded by distinct genes. However, the composition and function of tubulin isotypes in cilia are largely unclear. Here, we successfully labeled the endogenous α-tubulin and β-tubulin isotypes with HA or GFP tag in cultured mouse ependymal cells (EPCs) via the CRISPR/Cas9 system. TUBA1A, TUBA1B, TUBA1C, TUBB2A, TUBB2B, TUBB4B, and TUBB5 were identified to be incorporated in ependymal cilia, with TUBB4B showing the highest expression. Overexpression assay revealed that the ependymal cilia did not display a preference for the entrance of specific tubulin isotypes. Furthermore, luciferase reporter assay showed that the expression of TUBB4B in EPCs was specifically regulated by the ciliogenesis factor FOXJ1. TUBB4B deficiency disrupted planar polarity of EPCs and impaired cerebrospinal fluid flow, resulting in hydrocephalus. This study reveals the composition of tubulin isotypes in ependymal cilia and the specific role of FOXJ1-promoted TUBB4B in ciliary motility.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850445","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

Long-term management of body weight and physiological mechanisms of weight regain. 体重的长期管理和体重恢复的生理机制。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-03 DOI: 10.1093/jmcb/mjaf062

Tingting Hu, Yuqian Bao

{"title":"Long-term management of body weight and physiological mechanisms of weight regain.","authors":"Tingting Hu, Yuqian Bao","doi":"10.1093/jmcb/mjaf062","DOIUrl":"10.1093/jmcb/mjaf062","url":null,"abstract":"Overweight and obesity are major global health challenges. Despite progress in behavioral interventions, nutrition, physical activity, pharmacotherapy, and bariatric procedures, weight regain after successful weight loss is a major challenge. Understanding the definition and physiological mechanisms of weight regain is crucial for developing effective strategies to tackle weight regain and reduce cardiometabolic disorders. This review summarizes recent advances in weight loss strategies. We also discuss the metrics used to quantify weight regain, emphasizing the need for standardization to facilitate comparison between studies, and examine weight regain predictors, including demographic and clinical characteristics, behavior, anatomic factors, and biomarkers. The potential physiological mechanisms underlying weight regain, focusing on obesity memory, metabolic adaptation, and gut hormone alterations, are further elucidated. Comprehensively understanding weight regain provides a foundation for developing long-term, personalized strategies and integrating emerging technologies such as artificial intelligence into long-term weight management.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900550","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

A high-content phenotypic screen identifies luteolin as a repurposed drug to reduce pyruvate dehydrogenase phosphorylation and enhance energy production in CMTX6 cell models. 在CMTX6细胞模型中，高含量表型筛选鉴定木犀草素是一种减少丙酮酸脱氢酶磷酸化和增强能量产生的重新用途药物。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-03 DOI: 10.1093/jmcb/mjag012

Gonzalo Perez-Siles, Masahiro Nishide, Melina Ellis, Richard M Wynn, Gauri Shishodia, Steve Vucic, Marina L Kennerson

引用次数: 0

Correction to: Degradation of helicase-like transcription factor (HLTF) by ß-TrCP promotes hepatocarcinogenesis via activation of the p62/mTOR axis. 更正：ß-TrCP降解解旋酶样转录因子（HLTF）通过激活p62/mTOR轴促进肝癌的发生。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-07-03 DOI: 10.1093/jmcb/mjag032

引用次数: 0

Structural basis of complex assembly and nucleosome recognition by the chromatin remodeling ncBAF complex. 染色质重塑ncBAF复合体的复合体组装和核小体识别的结构基础。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-06-30 DOI: 10.1093/jmcb/mjag020

Wancheng Xu, Shengsheng Ma, Yi Li, Muchun Li, Chihang Li, Yue Yin, Qingrun Li, Jingdong Cheng, Yong Chen

{"title":"Structural basis of complex assembly and nucleosome recognition by the chromatin remodeling ncBAF complex.","authors":"Wancheng Xu, Shengsheng Ma, Yi Li, Muchun Li, Chihang Li, Yue Yin, Qingrun Li, Jingdong Cheng, Yong Chen","doi":"10.1093/jmcb/mjag020","DOIUrl":"https://doi.org/10.1093/jmcb/mjag020","url":null,"abstract":"BRG1/BRM-associated factor (BAF)-family chromatin remodelers regulate transcription and genome organization by repositioning nucleosomes. The human non-canonical BAF (ncBAF) complex is uniquely defined by the presence of BRD9 and GLTSCR1/GLTSCR1L, as well as the absence of the ARID1/2 scaffold and the canonical nucleosome-binding module found in cBAF and PBAF. How ncBAF assembles and engages nucleosomes remains elusive. Here, we present a cryo-EM structure of ncBAF bound to a nucleosome, integrated with biochemical assays and crosslinking mass spectrometry analyses. The ncBAF complex adopts a three-module architecture comprising an ATPase motor module, a repositioned actin-related protein (ARP) module, and a highly flexible Base module. The ncBAF-specific subunits BRD9 and GLTSCR1L are largely dispensable for complex assembly and nucleosome remodeling. Instead, BCL7A directly engages the H2A-H2B acidic patch and the H2A N-terminal tail, providing a structural substitute for SMARCB1 in stimulating remodeling activity. These findings reveal how ncBAF compensates for the loss of the canonical nucleosome-binding module through modular reorganization, providing a structural framework for understanding ncBAF-mediated chromatin regulation and its roles in development and disease.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352105","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

Microtubule-associated CCDC112 is essential for spermiogenesis and male fertility in mice. 微管相关的CCDC112对小鼠精子发生和雄性生育能力至关重要。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-06-25 DOI: 10.1093/jmcb/mjag019

Qingchao Li, Xirui Zi, Yue Lu, Hanxiao Yin, Qian Lyu, Junhao Han, Huixin Shen, Xiaoqian Meng, Shanshan Nai, Jun Zhou, Huijie Zhao, Ting Song

{"title":"Microtubule-associated CCDC112 is essential for spermiogenesis and male fertility in mice.","authors":"Qingchao Li, Xirui Zi, Yue Lu, Hanxiao Yin, Qian Lyu, Junhao Han, Huixin Shen, Xiaoqian Meng, Shanshan Nai, Jun Zhou, Huijie Zhao, Ting Song","doi":"10.1093/jmcb/mjag019","DOIUrl":"https://doi.org/10.1093/jmcb/mjag019","url":null,"abstract":"Defective sperm motility is frequently associated with male infertility. The immotile short-tail sperm (ISTS) defect is a rare condition in which most sperm cells have abnormally short tails, impairing their motility and leading to infertility. Despite its implications, the genetic factors related to the ISTS defect remain largely unclear. In this study, we identify coiled-coil domain-containing 112 (CCDC112) as a critical factor for sperm tail formation. CCDC112 can associate with microtubules and interact with multiple centrosomal proteins, including PCM1, TEX9, and taxilin. Disruption of CCDC112 expression profoundly affects the cellular distribution of PCM1. Interestingly, the knockout of Ccdc112 in mice impacts spermiogenesis, resulting in the ISTS defect and ultimately causing male infertility. Furthermore, quantitative proteomic analysis highlights the essential role of CCDC112 in regulating axonemal microtubule inner proteins. We thus characterize CCDC112 as a microtubule-associated protein and substantiate its genetic link to ISTS-related male infertility.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148330384","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