EMBO Reports最新文献_第8页

Publisher Correction: Cytoplasmic FBXO38 mediates PD-1 degradation. 出版商更正：细胞质 FBXO38 介导 PD-1 降解。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-12-01 DOI: 10.1038/s44319-024-00298-0

Xiwei Liu, Xiangbo Meng, Zuomiao Lin, Shutan Jiang, Haifeng Liu, Shao-Cong Sun, Xiaolong Liu, Penghui Zhou, Xiaowu Huang, Lai Wei, Wei Yang, Chenqi Xu

引用次数: 0

The Dectin-1 and Dectin-2 clusters: C-type lectin receptors with fundamental roles in immunity. Dectin-1 和 Dectin-2 簇：在免疫中发挥重要作用的 C 型凝集素受体。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-12-01 Epub Date: 2024-10-31 DOI: 10.1038/s44319-024-00296-2

Mariano Malamud, Gordon D Brown

{"title":"The Dectin-1 and Dectin-2 clusters: C-type lectin receptors with fundamental roles in immunity.","authors":"Mariano Malamud, Gordon D Brown","doi":"10.1038/s44319-024-00296-2","DOIUrl":"10.1038/s44319-024-00296-2","url":null,"abstract":"The ability of myeloid cells to recognize and differentiate endogenous or exogenous ligands rely on the presence of different transmembrane protein receptors. C-type lectin receptors (CLRs), defined by the presence of a conserved structural motif called C-type lectin-like domain (CTLD), are a crucial family of receptors involved in this process, being able to recognize a diverse range of ligands from glycans to proteins or lipids and capable of initiating an immune response. The Dectin-1 and Dectin-2 clusters involve two groups of CLRs, with genes genomically linked within the natural killer cluster of genes in both humans and mice, and all characterized by the presence of a single extracellular CTLD. Fundamental immune cell functions such as antimicrobial effector mechanisms as well as internalization and presentation of antigens are induced and/or regulated through activatory, or inhibitory signalling pathways triggered by these receptors after ligand binding. In this review, we will discuss the most recent concepts regarding expression, ligands, signaling pathways and functions of each member of the Dectin clusters of CLRs, highlighting the importance and diversity of their functions.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"5239-5264"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 novel bacterial effector protein mediates ER-LD membrane contacts to regulate host lipid droplets. 一种新型细菌效应蛋白介导 ER-LD 膜接触以调节宿主脂滴。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-12-01 Epub Date: 2024-09-27 DOI: 10.1038/s44319-024-00266-8

Rajendra Kumar Angara, Arif Sadi, Stacey D Gilk

{"title":"A novel bacterial effector protein mediates ER-LD membrane contacts to regulate host lipid droplets.","authors":"Rajendra Kumar Angara, Arif Sadi, Stacey D Gilk","doi":"10.1038/s44319-024-00266-8","DOIUrl":"10.1038/s44319-024-00266-8","url":null,"abstract":"Effective intracellular communication between cellular organelles occurs at dedicated membrane contact sites (MCSs). Tether proteins are responsible for the establishment of MCSs, enabling direct communication between organelles to ensure organelle function and host cell homeostasis. While recent research has identified tether proteins in several bacterial pathogens, their functions have predominantly been associated with mediating inter-organelle communication between the bacteria containing vacuole (BCV) and the host endoplasmic reticulum (ER). Here, we identify a novel bacterial effector protein, CbEPF1, which acts as a molecular tether beyond the confines of the BCV and facilitates interactions between host cell organelles. Coxiella burnetii, an obligate intracellular bacterial pathogen, encodes the FFAT motif-containing protein CbEPF1 which localizes to host lipid droplets (LDs). CbEPF1 establishes inter-organelle contact sites between host LDs and the ER through its interactions with VAP family proteins. Intriguingly, CbEPF1 modulates growth of host LDs in a FFAT motif-dependent manner. These findings highlight the potential for bacterial effector proteins to impact host cellular homeostasis by manipulating inter-organelle communication beyond conventional BCVs.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"5331-5351"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Eicosapentaenoic acid induces macrophage Mox polarization to prevent diabetic cardiomyopathy. 二十碳五烯酸诱导巨噬细胞 Mox 极化以预防糖尿病心肌病。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-12-01 Epub Date: 2024-10-31 DOI: 10.1038/s44319-024-00271-x

Jie Li, Wenshan Nan, Xiaoli Huang, Huali Meng, Shue Wang, Yan Zheng, Ying Li, Hui Li, Zhiyue Zhang, Lei Du, Xiao Yin, Hao Wu

{"title":"Eicosapentaenoic acid induces macrophage Mox polarization to prevent diabetic cardiomyopathy.","authors":"Jie Li, Wenshan Nan, Xiaoli Huang, Huali Meng, Shue Wang, Yan Zheng, Ying Li, Hui Li, Zhiyue Zhang, Lei Du, Xiao Yin, Hao Wu","doi":"10.1038/s44319-024-00271-x","DOIUrl":"10.1038/s44319-024-00271-x","url":null,"abstract":"Diabetic cardiomyopathy (DC) leads to heart failure, with few effective approaches for its intervention. Eicosapentaenoic acid (EPA) is an essential nutrient that benefits the cardiovascular system, but its effect on DC remains unknown. Here, we report that EPA protects against DC in streptozotocin and high-fat diet-induced diabetic mice, with an emphasis on the reduction of cardiac M1-polarized macrophages. In vitro, EPA abrogates cardiomyocyte injury induced by M1-polarized macrophages, switching macrophage phenotype from M1 to Mox, but not M2, polarization. Moreover, macrophage Mox polarization combats M1-polarized macrophage-induced cardiomyocyte injury. Further, heme oxygenase 1 (HO-1) was identified to maintain the Mox phenotype, mediating EPA suppression of macrophage M1 polarization and the consequential cardiomyocyte injury. Mechanistic studies reveal that G-protein-coupled receptor 120 mediates the upregulation of HO-1 by EPA. Notably, EPA promotes Mox polarization in monocyte-derived macrophages from diabetic patients. The current study provides EPA and macrophage Mox polarization as novel strategies for DC intervention.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"5507-5536"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

PARP1 condensates differentially partition DNA repair proteins and enhance DNA ligation. PARP1 缩合物可对 DNA 修复蛋白进行不同的分区，并增强 DNA 连接。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-12-01 Epub Date: 2024-11-04 DOI: 10.1038/s44319-024-00285-5

Christopher Chin Sang, Gaelen Moore, Maria Tereshchenko, Hongshan Zhang, Michael L Nosella, Morgan Dasovich, T Reid Alderson, Anthony K L Leung, Ilya J Finkelstein, Julie D Forman-Kay, Hyun O Lee

{"title":"PARP1 condensates differentially partition DNA repair proteins and enhance DNA ligation.","authors":"Christopher Chin Sang, Gaelen Moore, Maria Tereshchenko, Hongshan Zhang, Michael L Nosella, Morgan Dasovich, T Reid Alderson, Anthony K L Leung, Ilya J Finkelstein, Julie D Forman-Kay, Hyun O Lee","doi":"10.1038/s44319-024-00285-5","DOIUrl":"10.1038/s44319-024-00285-5","url":null,"abstract":"Poly(ADP-ribose) polymerase 1 (PARP1) is one of the first responders to DNA damage and plays crucial roles in recruiting DNA repair proteins through its activity - poly(ADP-ribosyl)ation (PARylation). The enrichment of DNA repair proteins at sites of DNA damage has been described as the formation of a biomolecular condensate. However, it remains unclear how exactly PARP1 and PARylation contribute to the formation and organization of DNA repair condensates. Using recombinant human single-strand repair proteins in vitro, we find that PARP1 readily forms viscous biomolecular condensates in a DNA-dependent manner and that this depends on its three zinc finger (ZnF) domains. PARylation enhances PARP1 condensation in a PAR chain length-dependent manner and increases the internal dynamics of PARP1 condensates. DNA and single-strand break repair proteins XRCC1, LigIII, Polβ, and FUS partition in PARP1 condensates, although in different patterns. While Polβ and FUS are both homogeneously mixed within PARP1 condensates, FUS enrichment is greatly enhanced upon PARylation whereas Polβ partitioning is not. XRCC1 and LigIII display an inhomogeneous organization within PARP1 condensates; their enrichment in these multiphase condensates is enhanced by PARylation. Functionally, PARP1 condensates concentrate short DNA fragments, which correlates with PARP1 clusters compacting long DNA and bridging DNA ends. Furthermore, the presence of PARP1 condensates significantly promotes DNA ligation upon PARylation. These findings provide insight into how PARP1 condensation and PARylation regulate the assembly and biochemical activities of DNA repair factors, which may inform on how PARPs function in DNA repair foci and other PAR-driven condensates in cells.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"5635-5666"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

PTGS is dispensable for the initiation of epigenetic silencing of an active transposon in Arabidopsis. 在拟南芥中，PTGS对于启动活性转座子的表观遗传沉默是不可或缺的。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-12-01 Epub Date: 2024-11-07 DOI: 10.1038/s44319-024-00304-5

Marieke Trasser, Grégoire Bohl-Viallefond, Verónica Barragán-Borrero, Laura Diezma-Navas, Lukas Loncsek, Magnus Nordborg, Arturo Marí-Ordóñez

{"title":"PTGS is dispensable for the initiation of epigenetic silencing of an active transposon in Arabidopsis.","authors":"Marieke Trasser, Grégoire Bohl-Viallefond, Verónica Barragán-Borrero, Laura Diezma-Navas, Lukas Loncsek, Magnus Nordborg, Arturo Marí-Ordóñez","doi":"10.1038/s44319-024-00304-5","DOIUrl":"10.1038/s44319-024-00304-5","url":null,"abstract":"Transposable elements (TEs) are repressed in plants through transcriptional gene silencing (TGS), maintained epigenetic silencing marks such as DNA methylation. However, the mechanisms by which silencing is first installed remain poorly understood in plants. Small interfering (si)RNAs and post-transcriptional gene silencing (PTGS) are believed to mediate the initiation of TGS by guiding the first deposition of DNA methylation. To determine how this silencing installation works, we took advantage of ÉVADÉ (EVD), an endogenous retroelement in Arabidopsis, able to recapitulate true de novo silencing with a sequence of PTGS followed by a TGS. To test whether PTGS is required for TGS, we introduce active EVD into RNA-DEPENDENT-RNA-POLYMERASE-6 (RDR6) mutants, an essential PTGS component. EVD activity and silencing are monitored across several generations. In the absence of PTGS, silencing of EVD is still achieved through installation of RNA-directed DNA methylation (RdDM). Our study shows that PTGS is dispensable for de novo EVD silencing. Although we cannot rule out that PTGS might facilitate TGS, or control TE activity, initiation of epigenetic silencing can take place in its absence.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"5780-5809"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 controversy around anti-amyloid antibodies for treating Alzheimer's disease : The European Medical Agency's ruling against the latest anti-amyloid drugs highlights the ongoing debate about their safety and efficacy. 围绕用于治疗阿尔茨海默病的抗淀粉样蛋白抗体的争议：欧洲医学机构针对最新抗淀粉样蛋白药物的规定凸显了对其安全性和有效性的持续争论。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-12-01 Epub Date: 2024-10-23 DOI: 10.1038/s44319-024-00294-4

Philip Hunter

引用次数: 0

Severe fever with thrombocytopenia syndrome virus induces lactylation of m6A reader protein YTHDF1 to facilitate viral replication. 严重发热伴血小板减少综合征病毒诱导 m6A 读取蛋白 YTHDF1 乳化，以促进病毒复制。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-12-01 Epub Date: 2024-11-04 DOI: 10.1038/s44319-024-00310-7

Bingxin Liu, Xiaoyan Tian, Linrun Li, Rui Zhang, Jing Wu, Na Jiang, Meng Yuan, Deyan Chen, Airong Su, Shijie Xu, Zhiwei Wu

{"title":"Severe fever with thrombocytopenia syndrome virus induces lactylation of m6A reader protein YTHDF1 to facilitate viral replication.","authors":"Bingxin Liu, Xiaoyan Tian, Linrun Li, Rui Zhang, Jing Wu, Na Jiang, Meng Yuan, Deyan Chen, Airong Su, Shijie Xu, Zhiwei Wu","doi":"10.1038/s44319-024-00310-7","DOIUrl":"10.1038/s44319-024-00310-7","url":null,"abstract":"Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging infectious pathogen with a high fatality rate, is an enveloped tripartite segmented single-stranded negative-sense RNA virus. SFTSV infection is characterized by suppressed host innate immunity, proinflammatory cytokine storm, failure of B-cell immunity, and robust viral replication. m6A modification has been shown to play a role in viral infections. However, interactions between m6A modification and SFTSV infection remain poorly understood. Through MeRIP-seq, we identify m6A modifications on SFTSV RNA. We show that YTHDF1 can bind to m6A modification sites on SFTSV, decreasing the stability of SFTSV RNA and reducing the translation efficiency of SFTSV proteins. The SFTSV virulence factor NSs increases lactylation of YTHDF1 and YTHDF1 degradation, thus facilitating SFTSV replication. Our findings indicate that the SFTSV protein NSs induce lactylation to inhibit YTHDF1 as a countermeasure to host's YTHDF1-mediated degradation of m6A-marked viral mRNAs.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"5599-5619"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Cultivating the next generation of leaders : How postdocs, principal investigators and institutes can nurture and select for leadership competencies. 培养下一代领导者：博士后、主要研究人员和研究机构如何培养和选拔领导能力。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-12-01 Epub Date: 2024-11-12 DOI: 10.1038/s44319-024-00308-1

James W Bryson, Ülkü Uzun, Victor O Oria, Jamie Y Auxillos, Iman Safari, Alexia M Lopresti, Agnieszka Krzyzanowska, Katrine Sonne-Hansen

引用次数: 0

Human PC4 supports telomere stability and viability in cells utilizing the alternative lengthening of telomeres mechanism. 人类 PC4 利用端粒替代性延长机制支持端粒稳定性和细胞活力。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1038/s44319-024-00295-3

Sara Salgado, Patricia L Abreu, Beatriz Moleirinho, Daniela S Guedes, Lee Larcombe, Claus M Azzalin

{"title":"Human PC4 supports telomere stability and viability in cells utilizing the alternative lengthening of telomeres mechanism.","authors":"Sara Salgado, Patricia L Abreu, Beatriz Moleirinho, Daniela S Guedes, Lee Larcombe, Claus M Azzalin","doi":"10.1038/s44319-024-00295-3","DOIUrl":"10.1038/s44319-024-00295-3","url":null,"abstract":"Cancer cells with an activated Alternative Lengthening of Telomeres (ALT) mechanism elongate telomeres via homology-directed repair. Sustained telomeric replication stress is an essential trigger of ALT activity; however, it can lead to cell death if not properly restricted. By analyzing publicly available data from genome-wide CRISPR KO screenings, we have identified the multifunctional protein PC4 as a novel factor essential for ALT cell viability. Depletion of PC4 results in rapid ALT cell death, while telomerase-positive cells show minimal effects. PC4 depletion induces replication stress and telomere fragility primarily in ALT cells, and increases ALT activity. PC4 binds to telomeric DNA in cells, and its binding can be enhanced by telomeric replication stress. Finally, a mutant PC4 with partly impaired single stranded DNA binding activity is capable to localize to telomeres and suppress ALT activity and telomeric replication stress. We propose that PC4 supports ALT cell viability, at least partly, by averting telomere dysfunction. Further studies of PC4 interactions at ALT telomeres may hold promise for innovative therapies to eradicate ALT cancers.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"5294-5315"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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