Journal of Molecular Cell Biology最新文献_第10页

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":" ","pages":""},"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

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":" ","pages":""},"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":" ","pages":""},"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":" ","pages":""},"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

Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR-Stat3/Akt pathway. 通过抑制表皮生长因子受体-Stat3/Akt通路，消耗Gsdma1/2/3可减轻PMA诱导的表皮增生。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1093/jmcb/mjad080

Qiyao Liu, Manyun Li, Minli Sun, Ruyue Xin, Yushu Wang, Qin Chen, Xiang Gao, Zhaoyu Lin

{"title":"Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR-Stat3/Akt pathway.","authors":"Qiyao Liu, Manyun Li, Minli Sun, Ruyue Xin, Yushu Wang, Qin Chen, Xiang Gao, Zhaoyu Lin","doi":"10.1093/jmcb/mjad080","DOIUrl":"10.1093/jmcb/mjad080","url":null,"abstract":"Homeostasis of the skin barrier is essential for maintaining normal skin function. Gasdermin A (GSDMA) is highly expressed in the skin and associated with many skin diseases, such as melanoma and psoriasis. In mice, GSDMA is encoded by three gene homologues, namely Gsdma1, Gsdma2, and Gsdma3. Although Gsdma3 gain-of-function mutations cause hair loss and skin inflammation, Gsdma3-deficient mice do not show any visible phenotypes in skin and hair structures. To explore the physiological function of GSDMA, we generated conventional Gsdma1/2/3 knockout (KO) mice. These mice showed significantly alleviated epidermal hyperplasia and inflammation induced by phorbol 12-myristate 13-acetate (PMA). Furthermore, the alleviation of epidermal hyperplasia depended on the expression of Gsdma1/2/3 specifically in keratinocytes. Mechanistically, Gsdma1/2/3 depletion downregulated epidermal growth factor receptor (EGFR) ligands, leading to the decreased EGFR-Stat3/Akt signalling. These results demonstrate that depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia partially by inhibiting the EGFR-Stat3/Akt pathway.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801509","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

HSD17B13 liquid–liquid phase separation promotes leukocyte adhesion in chronic liver inflammation HSD17B13液-液相分离促进慢性肝脏炎症中的白细胞粘附

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-05-02 DOI: 10.1093/jmcb/mjae018

Jing Ye, Xiyu Huang, Manman Yuan, Jinglin Wang, Ru Jia, Tianyi Wang, Yang Tan, Shun Zhu, Qiang Xu, Xingxin Wu

{"title":"HSD17B13 liquid–liquid phase separation promotes leukocyte adhesion in chronic liver inflammation","authors":"Jing Ye, Xiyu Huang, Manman Yuan, Jinglin Wang, Ru Jia, Tianyi Wang, Yang Tan, Shun Zhu, Qiang Xu, Xingxin Wu","doi":"10.1093/jmcb/mjae018","DOIUrl":"https://doi.org/10.1093/jmcb/mjae018","url":null,"abstract":"The rs72613567:TA polymorphism in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) has been found to reduce the progression from steatosis to nonalcoholic steatohepatitis. In this study, we sought to define the pathogenic role of HSD17B13 in triggering liver inflammation. Here we find that HSD17B13 forms liquid–liquid phase separation (LLPS) around lipid droplets in the livers of nonalcoholic steatohepatitis patients. The dimerization of HSD17B13 supports the LLPS formation and promotes its enzymatic function. HSD17B13 LLPS increases the biosynthesis of platelet activating factor (PAF), which in turn promotes fibrinogen synthesis and leukocyte adhesion. Blockade of PAFR or STAT3 pathway inhibited the fibrinogen synthesis and leukocyte adhesion. Importantly, adeno-associated viral-mediated xeno-expression of human HSD17B13 exacerbated western diet/carbon tetrachloride-induced liver inflammation in Hsd17b13−/− mice. In conclusion, our results suggest that HSD17B13 LLPS triggers liver inflammation by promoting PAF-mediated leukocyte adhesion, and targeting HSD17B13 phase transition could be a promising therapeutic approach for treating hepatic inflammation in chronic liver disease.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":"11 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840328","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

Highly efficient conversion of mouse fibroblasts into functional hepatic cells under chemical induction. 化学诱导下小鼠成纤维细胞高效转化为功能性肝细胞。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-10 DOI: 10.1093/jmcb/mjad071

Zhi Zhong, Jiangchuan Du, Xiangjie Zhu, Lingting Guan, Yanyu Hu, Peilin Zhang, Hongyang Wang

{"title":"Highly efficient conversion of mouse fibroblasts into functional hepatic cells under chemical induction.","authors":"Zhi Zhong, Jiangchuan Du, Xiangjie Zhu, Lingting Guan, Yanyu Hu, Peilin Zhang, Hongyang Wang","doi":"10.1093/jmcb/mjad071","DOIUrl":"10.1093/jmcb/mjad071","url":null,"abstract":"Previous studies have shown that hepatocyte-like cells can be generated from fibroblasts using either lineage-specific transcription factors or chemical induction methods. However, these methods have their own deficiencies that restrict the therapeutic applications of such induced hepatocytes. In this study, we present a transgene-free, highly efficient chemical-induced direct reprogramming approach to generate hepatocyte-like cells from mouse embryonic fibroblasts (MEFs). Using a small molecule cocktail (SMC) as an inducer, MEFs can be directly reprogrammed into hepatocyte-like cells, bypassing the intermediate stages of pluripotent and immature hepatoblasts. These chemical-induced hepatocyte-like cells (ciHeps) closely resemble mature primary hepatocytes in terms of morphology, biological behavior, gene expression patterns, marker expression levels, and hepatic functions. Furthermore, transplanted ciHeps can integrate into the liver, promote liver regeneration, and improve survival rates in mice with acute liver damage. ciHeps can also ameliorate liver fibrosis caused by chronic injuries and enhance liver function. Notably, ciHeps exhibit no tumorigenic potential either in vitro or in vivo. Mechanistically, SMC-induced mesenchymal-to-epithelial transition and suppression of SNAI1 contribute to the fate conversion of fibroblasts into ciHeps. These results indicate that this transgene-free, chemical-induced direct reprogramming technique has the potential to serve as a valuable means of producing alternative hepatocytes for both research and therapeutic purposes. Additionally, this method also sheds light on the direct reprogramming of other cell types under chemical induction.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11121195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299267","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 multiplexed time-resolved fluorescence resonance energy transfer ultrahigh-throughput screening assay for targeting the SMAD4-SMAD3-DNA complex. 针对SMAD4-SMAD3-DNA复合物的多路时间分辨荧光共振能量转移超高通量筛选试验

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-10 DOI: 10.1093/jmcb/mjad068

Wukun Ouyang, Qianjin Li, Qiankun Niu, Min Qui, Haian Fu, Yuhong Du, Xiulei Mo

{"title":"A multiplexed time-resolved fluorescence resonance energy transfer ultrahigh-throughput screening assay for targeting the SMAD4-SMAD3-DNA complex.","authors":"Wukun Ouyang, Qianjin Li, Qiankun Niu, Min Qui, Haian Fu, Yuhong Du, Xiulei Mo","doi":"10.1093/jmcb/mjad068","DOIUrl":"10.1093/jmcb/mjad068","url":null,"abstract":"The transforming growth factor-beta (TGFβ) signaling pathway plays crucial roles in the establishment of an immunosuppressive tumor microenvironment, making anti-TGFβ agents a significant area of interest in cancer immunotherapy. However, the clinical translation of current anti-TGFβ agents that target upstream cytokines and receptors remains challenging. Therefore, the development of small-molecule inhibitors specifically targeting SMAD4, the downstream master regulator of the TGFβ pathway, would offer an alternative approach with significant therapeutic potential for anti-TGFβ signaling. In this study, we present the development of a cell lysate-based multiplexed time-resolved fluorescence resonance energy transfer (TR-FRET) assay in an ultrahigh-throughput screening (uHTS) 1536-well plate format. This assay enables simultaneous monitoring of the protein‒protein interaction between SMAD4 and SMAD3, as well as the protein‒DNA interaction between SMADs and their consensus DNA-binding motif. The multiplexed TR-FRET assay exhibits high sensitivity, allowing the dynamic analysis of the SMAD4-SMAD3-DNA complex at single-amino acid resolution. Moreover, the multiplexed uHTS assay demonstrates robustness for screening small-molecule inhibitors. Through a pilot screening of an FDA-approved bioactive compound library, we identified gambogic acid and gambogenic acid as potential hit compounds. These proof-of-concept findings underscore the utility of our optimized multiplexed TR-FRET platform for large-scale screening to discover small-molecule inhibitors that target the SMAD4-SMAD3-DNA complex as novel anti-TGFβ signaling agents.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11063955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134649204","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