Journal of Molecular Cell Biology最新文献_第8页

Phase separation of SPIN1 through its IDR facilitates histone methylation readout and tumorigenesis. SPIN1 通过其 IDR 的相分离促进了组蛋白甲基化读出和肿瘤发生。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-11-25 DOI: 10.1093/jmcb/mjae024

Yukun Wang, Yuhan Chen, Mengyao Li, Jiayue Wang, Yuhan Jiang, Rong Xie, Yifeng Zhang, Zhihua Li, Zhenzhen Yan, Chen Wu

{"title":"Phase separation of SPIN1 through its IDR facilitates histone methylation readout and tumorigenesis.","authors":"Yukun Wang, Yuhan Chen, Mengyao Li, Jiayue Wang, Yuhan Jiang, Rong Xie, Yifeng Zhang, Zhihua Li, Zhenzhen Yan, Chen Wu","doi":"10.1093/jmcb/mjae024","DOIUrl":"10.1093/jmcb/mjae024","url":null,"abstract":"Spindlin1 (SPIN1) is a unique multivalent histone modification reader that plays a role in ribosomal RNA transcription, chromosome segregation, and tumorigenesis. However, the function of the extended N-terminal region of SPIN1 remains unclear. Here, we demonstrated that SPIN1 can form phase-separated and liquid-like condensates both in vitro and in vivo through its N-terminal intrinsically disordered region (IDR). The phase separation of SPIN1 recruits the histone methyltransferase MLL1 to the same condensates and enriches the H3K4 methylation marks. This process also facilitates the binding of SPIN1 to H3K4me3 and activates tumorigenesis-related genes. Moreover, SPIN1-IDR enhances the genome-wide chromatin binding of SPIN1 and facilitates its localization to genes associated with the MAPK signaling pathway. These findings provide new insights into the biological function of the IDR in regulating SPIN1 activity and reveal a previously unrecognized role of SPIN1-IDR in histone methylation readout. Our study uncovers the crucial role of appropriate biophysical properties of SPIN1 in facilitating gene expression and links phase separation to tumorigenesis, which provides a new perspective for understanding the function of SPIN1.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081543","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

Unleashing the power of antigen-presenting neutrophils. 释放抗原递呈中性粒细胞的力量

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-11-25 DOI: 10.1093/jmcb/mjae034

Yingcheng Wu, Jiaqiang Ma, Qiang Gao

引用次数: 0

Single-cell analysis defines LGALS1+ fibroblasts that promote proliferation and migration of intrahepatic cholangiocarcinoma. 单细胞分析确定了促进肝内胆管癌增殖和迁移的 LGALS1 + 成纤维细胞。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-11-25 DOI: 10.1093/jmcb/mjae023

Qiqi Cao, Jinxian Yang, Lixuan Jiang, Zhao Yang, Zhecai Fan, Shuzhen Chen, Sibo Zhu, Lei Yin, Hongyang Wang, Wen Wen

{"title":"Single-cell analysis defines LGALS1+ fibroblasts that promote proliferation and migration of intrahepatic cholangiocarcinoma.","authors":"Qiqi Cao, Jinxian Yang, Lixuan Jiang, Zhao Yang, Zhecai Fan, Shuzhen Chen, Sibo Zhu, Lei Yin, Hongyang Wang, Wen Wen","doi":"10.1093/jmcb/mjae023","DOIUrl":"10.1093/jmcb/mjae023","url":null,"abstract":"The incidence rate of intrahepatic cholangiocarcinoma (ICC), which has a poor prognosis, is rapidly increasing. To investigate the intratumor heterogeneity in ICC, we analyzed single-cell RNA sequencing data from the primary tumor and adjacent normal tissues of 14 treatment-naïve patients. We identified 10 major cell types, along with 45 subclusters of cells. Notably, we identified a fibroblast cluster, Fibroblast_LUM+, which was preferably enriched in tumor tissues and actively interacted with cholangiocytes. LGALS1 was verified as a marker gene of Fibroblast_LUM+, contributing to the malignant phenotype of ICC. Higher amount of LGALS1+ fibroblasts was associated with poorer overall survival of ICC patients. Mechanistically, LGALS1+ fibroblasts activated the proliferation and migration of tumor cells by upregulating the expression levels of CCR2, ADAM15, and β-integrin. Silencing LGALS1 in cancer-associated fibroblasts (CAFs) suppressed CAF-augmented tumor cell migration and invasion in vitro as well as tumor formation in vivo, suggesting that blockade of LGALS1 serves as a potential therapeutic approach for ICC. Taken together, our single-cell analysis provides insight into the interaction between malignant cells and specific subtypes of fibroblasts, which contributes to better understanding of the intratumor heterogeneity in ICC and the development of novel strategies for the treatment of ICC by targeting fibroblasts in the tumor microenvironment.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11639627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306094","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

CCT6A alleviates pulmonary fibrosis by inhibiting HIF-1α-mediated lactate production. CCT6A通过抑制HIF-1α介导的乳酸生成减轻肺纤维化。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-21 DOI: 10.1093/jmcb/mjae021

Peishuo Yan, Kun Yang, Mengwei Xu, Miaomiao Zhu, Yudi Duan, Wenwen Li, Lulu Liu, Chenxi Liang, Zhongzheng Li, Xin Pan, Lan Wang, Guoying Yu

{"title":"CCT6A alleviates pulmonary fibrosis by inhibiting HIF-1α-mediated lactate production.","authors":"Peishuo Yan, Kun Yang, Mengwei Xu, Miaomiao Zhu, Yudi Duan, Wenwen Li, Lulu Liu, Chenxi Liang, Zhongzheng Li, Xin Pan, Lan Wang, Guoying Yu","doi":"10.1093/jmcb/mjae021","DOIUrl":"10.1093/jmcb/mjae021","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a lethal progressive fibrotic lung disease. The development of IPF involves different molecular and cellular processes, and recent studies indicate that lactate plays a significant role in promoting the progression of the disease. Nevertheless, the mechanism by which lactate metabolism is regulated and the downstream effects remain unclear. The molecular chaperone CCT6A performs multiple functions in a variety of biological processes. Our research has identified a potential association between CCT6A and serum lactate levels in IPF patients. Herein, we found that CCT6A was highly expressed in type 2 alveolar epithelial cells (AEC2s) of fibrotic lung tissues and correlated with disease severity. Lactate increases the accumulation of lipid droplets in epithelial cells. CCT6A inhibits lipid synthesis by blocking the production of lactate in AEC2s and alleviates bleomycin-induced pulmonary fibrosis in mice. In addition, our results revealed that CCT6A blocks HIF-1α-mediated lactate production by driving the VHL-dependent ubiquitination and degradation of HIF-1α and further inhibits lipid accumulation in fibrotic lungs. In conclusion, we propose that there is a pivotal regulatory role of CCT6A in lactate metabolism in pulmonary fibrosis, and strategies aimed at targeting these key molecules could represent potential therapeutic approaches for pulmonary fibrosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957738","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

Structure-specific nucleases in genome dynamics and strategies for targeting cancers. 基因组动态中的结构特异性核酸酶和针对癌症的策略。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-21 DOI: 10.1093/jmcb/mjae019

Haitao Sun, Megan Luo, Mian Zhou, Li Zheng, Hongzhi Li, R Steven Esworthy, Binghui Shen

{"title":"Structure-specific nucleases in genome dynamics and strategies for targeting cancers.","authors":"Haitao Sun, Megan Luo, Mian Zhou, Li Zheng, Hongzhi Li, R Steven Esworthy, Binghui Shen","doi":"10.1093/jmcb/mjae019","DOIUrl":"10.1093/jmcb/mjae019","url":null,"abstract":"Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in genomes. They widely vary in substrates, causing differentiation in cleavage patterns and having a diversified role in maintaining genetic material. Through cellular evolution of prokaryotic to eukaryotic, nucleases become structure-specific in recognizing its own or foreign genomic DNA/RNA configurations as its substrates, including flaps, bubbles, and Holliday junctions. These special structural configurations are commonly found as intermediates in processes like DNA replication, repair, and recombination. The structure-specific nature and diversified functions make them essential to maintaining genome integrity and evolution in normal and cancer cells. In this article, we review their roles in various pathways, including Okazaki fragment maturation during DNA replication, end resection in homology-directed recombination repair of DNA double-strand breaks, DNA excision repair and apoptosis DNA fragmentation in response to exogenous DNA damage, and HIV life cycle. As the nucleases serve as key points for the DNA dynamics, cellular apoptosis, and cancer cell survival pathways, we discuss the efforts in the field in developing the therapeutic regimens, taking advantage of recently available knowledge of their diversified structures and functions.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876596","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 preserves quiescent microtubule functions by dual-end capping. CSPP1 通过双端封顶来保护静态微管功能

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-21 DOI: 10.1093/jmcb/mjae022

Marina Mapelli

引用次数: 0

Sympathetic nerve signals: orchestrators of mammary development and stem cell vitality. 交感神经信号：乳腺发育和干细胞活力的协调者。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-21 DOI: 10.1093/jmcb/mjae020

Zi Ye, Yu Xu, Mengna Zhang, Cheguo Cai

{"title":"Sympathetic nerve signals: orchestrators of mammary development and stem cell vitality.","authors":"Zi Ye, Yu Xu, Mengna Zhang, Cheguo Cai","doi":"10.1093/jmcb/mjae020","DOIUrl":"10.1093/jmcb/mjae020","url":null,"abstract":"The mammary gland is a dynamic organ that undergoes significant changes at multiple stages of postnatal development. Although the roles of systemic hormones and microenvironmental cues in mammary homeostasis have been extensively studied, the influence of neural signals, particularly those from the sympathetic nervous system, remains poorly understood. Here, using a mouse mammary gland model, we delved into the regulatory role of sympathetic nervous signaling in the context of mammary stem cells and mammary development. Our findings revealed that depletion of sympathetic nerve signals results in defective mammary development during puberty, adulthood, and pregnancy, accompanied by a reduction in mammary stem cell numbers. Through in vitro three-dimensional culture and in vivo transplantation analyses, we demonstrated that the absence of sympathetic nerve signals hinders mammary stem cell self-renewal and regeneration, while activation of sympathetic nervous signaling promotes these capacities. Mechanistically, sympathetic nerve signals orchestrate mammary stem cell activity and mammary development through the extracellular signal-regulated kinase signaling pathway. Collectively, our study unveils the crucial roles of sympathetic nerve signals in sustaining mammary development and regulating mammary stem cell activity, offering a novel perspective on the involvement of the nervous system in modulating adult stem cell function and organ development.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916900","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 FAcilitates Chromatin Transcription complex regulates the ratio of glycolysis to oxidative phosphorylation in neural stem cells. FAcilitates 染色质转录复合物调节神经干细胞中糖酵解与氧化磷酸化的比例。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-09-30 DOI: 10.1093/jmcb/mjae017

Yuhan Lou, Litao Wu, Wanlin Cai, Huan Deng, Rong Sang, Shanshan Xie, Xiao Xu, Xin Yuan, Cheng Wu, Man Xu, Wanzhong Ge, Yongmei Xi, Xiaohang Yang

{"title":"The FAcilitates Chromatin Transcription complex regulates the ratio of glycolysis to oxidative phosphorylation in neural stem cells.","authors":"Yuhan Lou, Litao Wu, Wanlin Cai, Huan Deng, Rong Sang, Shanshan Xie, Xiao Xu, Xin Yuan, Cheng Wu, Man Xu, Wanzhong Ge, Yongmei Xi, Xiaohang Yang","doi":"10.1093/jmcb/mjae017","DOIUrl":"10.1093/jmcb/mjae017","url":null,"abstract":"Defects in the FAcilitates Chromatin Transcription (FACT) complex, a histone chaperone composed of SSRP1 and SUPT16H, are implicated in intellectual disability. Here, we reveal that the FACT complex promotes glycolysis and sustains the correct cell fate of neural stem cells/neuroblasts in the Drosophila 3rd instar larval central brain. We show that the FACT complex binds to the promoter region of the estrogen-related receptor (ERR) gene and positively regulates ERR expression. ERR is known to act as an aerobic glycolytic switch by upregulating the enzymes required for glycolysis. Dysfunction of the FACT complex leads to the downregulation of ERR transcription, resulting in a decreased ratio of glycolysis to oxidative phosphorylation (G/O) in neuroblasts. Consequently, neuroblasts exhibit smaller cell sizes, lower proliferation potential, and altered cell fates. Overexpression of ERR or suppression of mitochondrial oxidative phosphorylation in neuroblasts increases the relative G/O ratio and rescues defective phenotypes caused by dysfunction of the FACT complex. Thus, the G/O ratio, mediated by the FACT complex, plays a crucial role in neuroblast cell fate maintenance. Our study may shed light on the mechanism by which mutations in the FACT complex lead to intellectual disability in humans.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891908","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

Synergistic regulation of fusion pore opening and dilation by SNARE and synaptotagmin-1. SNARE 和 synaptotagmin-1 对融合孔开放和扩张的协同调控。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-09-30 DOI: 10.1093/jmcb/mjae011

Kaiju Li, Kaiyu Li, Jiaqi Fan, Xing Zhang, Chengyan Tao, Yijuan Xiang, Lele Cui, Hao Li, Minghan Li, Yanjing Zhang, Jia Geng, Ying Lai

{"title":"Synergistic regulation of fusion pore opening and dilation by SNARE and synaptotagmin-1.","authors":"Kaiju Li, Kaiyu Li, Jiaqi Fan, Xing Zhang, Chengyan Tao, Yijuan Xiang, Lele Cui, Hao Li, Minghan Li, Yanjing Zhang, Jia Geng, Ying Lai","doi":"10.1093/jmcb/mjae011","DOIUrl":"10.1093/jmcb/mjae011","url":null,"abstract":"Fusion pore opening is a transient intermediate state of synaptic vesicle exocytosis, which is highly dynamic and precisely regulated by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex and synaptotagmin-1 (Syt1). Yet, the regulatory mechanism is not fully understood. In this work, using single-channel membrane fusion electrophysiology, we determined that SNAREpins are important for driving fusion pore opening and dilation but incapable of regulating the dynamics. When Syt1 was added, the closing frequency of fusion pores significantly increased, while the radius of fusion pores mildly decreased. In response to Ca2+, SNARE/Syt1 greatly increased the radius of fusion pores and reduced their closing frequency. Moreover, the residue F349 in the C2B domain of Syt1, which mediates Syt1 oligomerization, was required for clamping fusion pore opening in the absence of Ca2+, probably by extending the distance between the two membranes. Finally, in Ca2+-triggered fusion, the primary interface between SNARE and Syt1 plays a critical role in stabilizing and dilating the fusion pore, while the polybasic region of Syt1 C2B domain has a mild effect on increasing the radius of the fusion pore. In summary, our results suggest that Syt1, SNARE, and the anionic membrane synergically orchestrate the dynamics of fusion pore opening in synaptic vesicle exocytosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039644","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

Chromothripsis: an emerging crossroad from aberrant mitosis to therapeutic opportunities. 染色体三分裂：从异常有丝分裂到治疗机会的新兴十字路口。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-09-30 DOI: 10.1093/jmcb/mjae016

Umer Ejaz, Zhen Dou, Phil Y Yao, Zhikai Wang, Xing Liu, Xuebiao Yao

{"title":"Chromothripsis: an emerging crossroad from aberrant mitosis to therapeutic opportunities.","authors":"Umer Ejaz, Zhen Dou, Phil Y Yao, Zhikai Wang, Xing Liu, Xuebiao Yao","doi":"10.1093/jmcb/mjae016","DOIUrl":"10.1093/jmcb/mjae016","url":null,"abstract":"Chromothripsis, a type of complex chromosomal rearrangement originally known as chromoanagenesis, has been a subject of extensive investigation due to its potential role in various diseases, particularly cancer. Chromothripsis involves the rapid acquisition of tens to hundreds of structural rearrangements within a short period, leading to complex alterations in one or a few chromosomes. This phenomenon is triggered by chromosome mis-segregation during mitosis. Errors in accurate chromosome segregation lead to formation of aberrant structural entities such as micronuclei or chromatin bridges. The association between chromothripsis and cancer has attracted significant interest, with potential implications for tumorigenesis and disease prognosis. This review aims to explore the intricate mechanisms and consequences of chromothripsis, with a specific focus on its association with mitotic perturbations. Herein, we discuss a comprehensive analysis of crucial molecular entities and pathways, exploring the intricate roles of the CIP2A-TOPBP1 complex, micronuclei formation, chromatin bridge processing, DNA damage repair, and mitotic checkpoints. Moreover, the review will highlight recent advancements in identifying potential therapeutic targets and the underlying molecular mechanisms associated with chromothripsis, paving the way for future therapeutic interventions in various diseases.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863118","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