Journal of Molecular Cell Biology最新文献

{"title":"A G protein γ subunit regulates crop alkaline sensitivity by modulating H2O2 transporter PIP2s.","authors":"Feifei Yu, Cuixia Liu, Huili Zhang, Qi Xie","doi":"10.1093/jmcb/mjad020","DOIUrl":"10.1093/jmcb/mjad020","url":null,"abstract":"to global food security and","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0f/07/mjad020.PMC10500545.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10249395","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":"SARS-CoV-2 spike variants differ in their allosteric responses to linoleic acid.","authors":"A Sofia F Oliveira, Deborah K Shoemark, Andrew D Davidson, Imre Berger, Christiane Schaffitzel, Adrian J Mulholland","doi":"10.1093/jmcb/mjad021","DOIUrl":"10.1093/jmcb/mjad021","url":null,"abstract":"<p><p>The SARS-CoV-2 spike protein contains a functionally important fatty acid (FA) binding site, which is also found in some other coronaviruses, e.g. SARS-CoV and MERS-CoV. The occupancy of the FA site by linoleic acid (LA) reduces infectivity by 'locking' the spike in a less infectious conformation. Here, we use dynamical-nonequilibrium molecular dynamics (D-NEMD) simulations to compare the allosteric responses of spike variants to LA removal. D-NEMD simulations show that the FA site is coupled to other functional regions of the protein, e.g. the receptor-binding motif (RBM), N-terminal domain (NTD), furin cleavage site, and regions surrounding the fusion peptide. D-NEMD simulations also identify the allosteric networks connecting the FA site to these functional regions. The comparison between the wild-type spike and four variants (Alpha, Delta, Delta plus, and Omicron BA.1) shows that the variants differ significantly in their responses to LA removal. The allosteric connections to the FA site on Alpha are generally similar to those on the wild-type protein, with the exception of the RBM and the S71-R78 region, which show a weaker link to the FA site. In contrast, Omicron is the most different variant, exhibiting significant differences in the RBM, NTD, V622-L629, and furin cleavage site. These differences in the allosteric modulation may be of functional relevance, potentially affecting transmissibility and virulence. Experimental comparison of the effects of LA on SARS-CoV-2 variants, including emerging variants, is warranted.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182838","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":"Corrigendum to 'microRNA-21a-5p/PDCD4 axis regulates mesenchymal stem cell-induced neuroprotection in acute glaucoma'.","authors":"Wenru Su, Zuohong Li, Yu Jia, Yingting Zhu, Wenjia Cai, Peixing Wan, Yingying Zhang, Song Guo Zheng, Yehong Zhuo","doi":"10.1093/jmcb/mjad028","DOIUrl":"10.1093/jmcb/mjad028","url":null,"abstract":"In this article","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92154782","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":"Comments on 'Downregulation of hepatic ceruloplasmin ameliorates NAFLD via SCO1-AMPK-LKB1 complex'.","authors":"Sijia Lu, Suzhen Chen, Ji Miao, Junli Liu","doi":"10.1093/jmcb/mjad026","DOIUrl":"10.1093/jmcb/mjad026","url":null,"abstract":"","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bf/10/mjad026.PMC10483445.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10187229","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":"Accurate prediction of pan-cancer types using machine learning with minimal number of DNA methylation sites.","authors":"Wei Ning, Tao Wu, Chenxu Wu, Shixiang Wang, Ziyu Tao, Guangshuai Wang, Xiangyu Zhao, Kaixuan Diao, Jinyu Wang, Jing Chen, Fuxiang Chen, Xue-Song Liu","doi":"10.1093/jmcb/mjad023","DOIUrl":"10.1093/jmcb/mjad023","url":null,"abstract":"<p><p>DNA methylation analysis has been applied to determine the primary site of cancer; however, robust and accurate prediction of cancer types with a minimum number of sites is still a significant scientific challenge. To build an accurate and robust cancer type prediction tool with a minimum number of DNA methylation sites, we internally benchmarked different DNA methylation site selection and ranking procedures, as well as different classification models. We used The Cancer Genome Atlas dataset (26 cancer types with 8296 samples) to train and test models and used an independent dataset (17 cancer types with 2738 samples) for model validation. A deep neural network model using a combined feature selection procedure (named MethyDeep) can predict 26 cancer types using 30 methylation sites with superior performance compared with the known methods for both primary and metastatic cancers in independent validation datasets. In conclusion, MethyDeep is an accurate and robust cancer type predictor with the minimum number of DNA methylation sites; it could help the cost-effective clarification of cancer of unknown primary patients and the liquid biopsy-based early screening of cancers.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10635511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9273321","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":"An integrative profiling of metabolome and transcriptome in the plasma and skeletal muscle following an exercise intervention in diet-induced obese mice.","authors":"Shuang Han,&nbsp;Qingqian Wu,&nbsp;Mengying Wang,&nbsp;Miqi Yang,&nbsp;Chen Sun,&nbsp;Jiaqi Liang,&nbsp;Xiaozhen Guo,&nbsp;Zheyu Zhang,&nbsp;Jingya Xu,&nbsp;Xinyuan Qiu,&nbsp;Cen Xie,&nbsp;Siyu Chen,&nbsp;Yue Gao,&nbsp;Zhuo-Xian Meng","doi":"10.1093/jmcb/mjad016","DOIUrl":"10.1093/jmcb/mjad016","url":null,"abstract":"<p><p>Exercise intervention at the early stage of type 2 diabetes mellitus (T2DM) can aid in the maintenance of blood glucose homeostasis and prevent the development of macrovascular and microvascular complications. However, the exercise-regulated pathways that prevent the development of T2DM remain largely unclear. In this study, two forms of exercise intervention, treadmill training and voluntary wheel running, were conducted for high-fat diet (HFD)-induced obese mice. We observed that both forms of exercise intervention alleviated HFD-induced insulin resistance and glucose intolerance. Skeletal muscle is recognized as the primary site for postprandial glucose uptake and for responsive alteration beyond exercise training. Metabolomic profiling of the plasma and skeletal muscle in Chow, HFD, and HFD-exercise groups revealed robust alterations in metabolic pathways by exercise intervention in both cases. Overlapping analysis identified nine metabolites, including beta-alanine, leucine, valine, and tryptophan, which were reversed by exercise treatment in both the plasma and skeletal muscle. Transcriptomic analysis of gene expression profiles in the skeletal muscle revealed several key pathways involved in the beneficial effects of exercise on metabolic homeostasis. In addition, integrative transcriptomic and metabolomic analyses uncovered strong correlations between the concentrations of bioactive metabolites and the expression levels of genes involved in energy metabolism, insulin sensitivity, and immune response in the skeletal muscle. This work established two models of exercise intervention in obese mice and provided mechanistic insights into the beneficial effects of exercise intervention on systemic energy homeostasis.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9112969","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":"CSF2 upregulates CXCL3 expression in adipocytes to promote metastasis of breast cancer via the FAK signaling pathway.","authors":"Xi He, Lieliang Wang, Honghui Li, Yaru Liu, Chang Tong, Caifeng Xie, Xiaohua Yan, Daya Luo, Xiangyang Xiong","doi":"10.1093/jmcb/mjad025","DOIUrl":"10.1093/jmcb/mjad025","url":null,"abstract":"<p><p>Recent studies have demonstrated that cancer-associated adipocytes (CAAs) in the tumor microenvironment are involved in the malignant progression of breast cancer. However, the underlying mechanism of CAA formation and its effects on the development of breast cancer are still unknown. Here, we show that CSF2 is highly expressed in both CAAs and breast cancer cells. CSF2 promotes inflammatory phenotypic changes of adipocytes through the Stat3 signaling pathway, leading to the secretion of multiple cytokines and proteases, particularly C-X-C motif chemokine ligand 3 (CXCL3). Adipocyte-derived CXCL3 binds to its specific receptor CXCR2 on breast cancer cells and activates the FAK pathway, enhancing the mesenchymal phenotype, migration, and invasion of breast cancer cells. In addition, a combination treatment targeting CSF2 and CXCR2 shows a synergistic inhibitory effect on adipocyte-induced lung metastasis of mouse 4T1 cells in vivo. These findings elucidate a novel mechanism of breast cancer metastasis and provide a potential therapeutic strategy for breast cancer metastasis.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9376577","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":"METTL3-mediated m6A modification of HMGA2 mRNA promotes subretinal fibrosis and epithelial-mesenchymal transition.","authors":"Yuwei Wang,&nbsp;Yuhong Chen,&nbsp;Jian Liang,&nbsp;Mei Jiang,&nbsp;Ting Zhang,&nbsp;Xiaoling Wan,&nbsp;Jiahui Wu,&nbsp;Xiaomeng Li,&nbsp;Jieqiong Chen,&nbsp;Junran Sun,&nbsp;Yifan Hu,&nbsp;Peirong Huang,&nbsp;Jingyang Feng,&nbsp;Te Liu,&nbsp;Xiaodong Sun","doi":"10.1093/jmcb/mjad005","DOIUrl":"10.1093/jmcb/mjad005","url":null,"abstract":"<p><p>Subretinal fibrosis is a major cause of the poor visual prognosis for patients with neovascular age-related macular degeneration (nAMD). Myofibroblasts originated from retinal pigment epithelial (RPE) cells through epithelial-mesenchymal transition (EMT) contribute to the fibrosis formation. N6-Methyladenosine (m6A) modification has been implicated in the EMT process and multiple fibrotic diseases. The role of m6A modification in EMT-related subretinal fibrosis has not yet been elucidated. In this study, we found that during subretinal fibrosis in the mouse model of laser-induced choroidal neovascularization, METTL3 was upregulated in RPE cells. Through m6A epitranscriptomic microarray and further verification, high-mobility group AT-hook 2 (HMGA2) was identified as the key downstream target of METTL3, subsequently activating potent EMT-inducing transcription factor SNAIL. Finally, by subretinal injections of adeno-associated virus vectors, we confirmed that METTL3 deficiency in RPE cells could efficiently attenuate subretinal fibrosis in vivo. In conclusion, our present research identified an epigenetic mechanism of METTL3-m6A-HMGA2 in subretinal fibrosis and EMT of RPE cells, providing a novel therapeutic target for subretinal fibrosis secondary to nAMD.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9509338","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":"SARS-CoV-2 main protease Nsp5 cleaves and inactivates human tRNA methyltransferase TRMT1.","authors":"Jia-Li Lu,&nbsp;Xiao-Long Zhou","doi":"10.1093/jmcb/mjad024","DOIUrl":"10.1093/jmcb/mjad024","url":null,"abstract":"is crucial for tRNA structure and function. TRMT1 is localized in the nucleus, cytoplasm, and mitochondria. Its mitochondrial localization is mediated by an N-terminal mitochondrial targeting sequence ( MTS ) of ∼35 residues ( Dewe et al., 2017 ) . However, it is not known whether TRMT1 is a bone-fide substrate of Nsp5. Moreover, the consequence of the potential cleavage remains unclear. Here, we expressed and purified a recombinant SARS-CoV-2 Nsp5 with a C-terminal His 6 tag and an MTS-deleted TRMT1 with an N-terminal FLAG and a C-terminal His 6 tag ( TRMT1 35 ) using Escherichia coli ( Figure 1 A; Supplementary Figure S1 A and B ) . Western blot analysis using anti-FLAG antibodies showed that the amount of TRMT1 35 decreased after incubation with Nsp5 in a dose-dependent manner, accompanied by the appearance of a digested product of ∼58 kDa ( Figure 1 B ) , suggesting that the cleavage site is in the latter part of TRMT1. However, the C-terminal cleavage product with a lower molecular weight was not observed using anti-His 6 antibodies. Coomassie blue staining using the same protein samples and digestion conditions also showed a clear cleaved fragment after incubation with Nsp5 ( Supplementary Figure S1 C ) . To confirm the digestion of TRMT1 by SARS-CoV-2 Nsp5 in vivo , we co-expressed TRMT1 35 ( with N-terminal HA and C-terminal FLAG tags ) and 3 × Myc-tagged Nsp5 ( Figure 1 A ) in HEK293T cells. Indeed, western blot analysis using anti-HA antibodies showed the generation of a digested product of ∼58 kDa, while the cleaved fragment with the lower molecular mass was likewise invisible ( Figure 1 C ) . Considering the high sequence identity ( ∼96% ) between SARS-CoV-2 Nsp5 and SARS-CoV Nsp5, we further purified SARS-CoV Nsp5 ( Supplementary Figure S1 D ) . Consistently, SARS-CoV Nsp5 was also able to digest TRMT1 35 in vitro with a high efficiency ( Figure 1 D ) , indicating that TRMT1 cleavage is a conserved mechanism among different CoVs. To better understand whether TRMT1 digestion is mediated by the protease activity of Nsp5, the C145 residue of SARS-CoV-2 Nsp5 was replaced by alanine, resulting in a C145A mutant that was defective in cleavage ( Figure 1 E ) . The C145A mutant is a well-known variant that was constructed to show the contribution of the C145–H41 catalytic dyad to substrate cleavage ( Jin et al., 2020 ) . The C145A mutant exhibits the same three-dimensional structure as the wild-type enzyme ( Hsu et al., 2005 ) . These data clearly demonstrated that Nsp5 is able to cleave TRMT1 in vitro and in vivo via its protease activity. Subsequently, we intended to identify the cleavage site in TRMT1. Nsp5 digests all protein substrates at conserved glutamine residues. NetCorona 1.0, a website predicting Nsp5 cleavage sites ( Kiemer et al., 2004 ) , showed that Q530 was the only confident candidate with a high score of 0.942, while other glutamine residues ( such as Q584 ) were excluded ( Supplementary Figure S2 A ) . This prediction was","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/30/85/mjad024.PMC10399916.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10371371","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 actin-bundling protein Fascin-1 modulates ciliary signalling.","authors":"Lena Brücker,&nbsp;Stefanie Kornelia Becker,&nbsp;Vanessa Maissl,&nbsp;Gregory Harms,&nbsp;Maddy Parsons,&nbsp;Helen Louise May-Simera","doi":"10.1093/jmcb/mjad022","DOIUrl":"10.1093/jmcb/mjad022","url":null,"abstract":"<p><p>Primary cilia are microtubule-based cell organelles important for cellular communication. Since they are involved in the regulation of numerous signalling pathways, defects in cilia development or function are associated with genetic disorders, collectively called ciliopathies. Besides their ciliary functions, recent research has shown that several ciliary proteins are involved in the coordination of the actin cytoskeleton. Although ciliary and actin phenotypes are related, the exact nature of their interconnection remains incompletely understood. Here, we show that the protein BBS6, associated with the ciliopathy Bardet-Biedl syndrome, cooperates with the actin-bundling protein Fascin-1 in regulating filopodia and ciliary signalling. We found that loss of Bbs6 affects filopodia length potentially via attenuated interaction with Fascin-1. Conversely, loss of Fascin-1 leads to a ciliary phenotype, subsequently affecting ciliary Wnt signalling, possibly in collaboration with BBS6. Our data shed light on how ciliary proteins are involved in actin regulations and provide new insight into the involvement of the actin regulator Fascin-1 in ciliogenesis and cilia-associated signalling. Advancing our knowledge of the complex regulations between primary cilia and actin dynamics is important to understand the pathogenic consequences of ciliopathies.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10485897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10644319","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}