EMBO Reports最新文献_第3页

Under pressure. 在压力下。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-18 DOI: 10.1038/s44319-025-00419-3

Bernd Pulverer

引用次数: 0

Molecular biology and design research : A new paradigm and transdisciplinary approach to communicating science. 分子生物学与设计研究：科学交流的新范式与跨学科方法。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-31 DOI: 10.1038/s44319-025-00434-4

Carla Molins-Pitarch, Jonas Krebs, David Brena

引用次数: 0

What must not be named : Facts, emotions and coping strategies to enhance animal welfare in research. 不能命名的：事实、情绪和应对策略，以提高研究中的动物福利。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-31 DOI: 10.1038/s44319-025-00429-1

Katarina Riesner, Linda Hammerich, Denise Jahn, Agnes Ellinghaus, Dietrich Polenz, Lisa Grohmann, Juliane K Unger

引用次数: 0

HDAC6 deacetylates ENKD1 to regulate mitotic spindle behavior and corneal epithelial homeostasis. HDAC6使ENKD1去乙酰化，调节有丝分裂纺锤体行为和角膜上皮稳态。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-28 DOI: 10.1038/s44319-025-00438-0

Ting Song, Xueqing Han, Hanxiao Yin, Junkui Zhao, Mingming Ma, Xiaonuan Wen, Chunli Liu, Yiyang Yue, Huijie Zhao, Jun Zhou, Yang Yang, Jie Ran, Min Liu

{"title":"HDAC6 deacetylates ENKD1 to regulate mitotic spindle behavior and corneal epithelial homeostasis.","authors":"Ting Song, Xueqing Han, Hanxiao Yin, Junkui Zhao, Mingming Ma, Xiaonuan Wen, Chunli Liu, Yiyang Yue, Huijie Zhao, Jun Zhou, Yang Yang, Jie Ran, Min Liu","doi":"10.1038/s44319-025-00438-0","DOIUrl":"10.1038/s44319-025-00438-0","url":null,"abstract":"Corneal diseases can cause severe visual impairment and even blindness, which have been linked to the interruption of corneal epithelial homeostasis. However, the underlying molecular mechanisms are largely unknown. In this study, by comparing the transcriptomes of keratoconus, bacterial keratitis, viral keratitis, and healthy corneas, we found a steady upregulation of histone deacetylase 6 (HDAC6) in corneal diseases. Consistently, a significant increase in HDAC6 was observed in mouse corneas with bacterial keratitis. Overexpression of HDAC6 in mice results in a significant thickening of the corneal epithelium. Mechanistic studies reveal that HDAC6 overexpression disrupts mitotic spindle orientation and positioning in corneal epithelial cells. Our data further show that HDAC6 deacetylates enkurin domain-containing protein 1 (ENKD1) at lysine 98 and thereby impedes its interaction with γ-tubulin, restraining the centrosomal localization of ENKD1 and its proper function in regulating mitotic spindle behavior. These findings uncover a pivotal role for HDAC6-mediated deacetylation of ENKD1 in the control of corneal epithelial homeostasis, providing potential therapeutic targets for treating corneal diseases.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Syndecans and glycosaminoglycans influence B-cell development and activation. Syndecans和糖胺聚糖影响b细胞的发育和活化。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-28 DOI: 10.1038/s44319-025-00432-6

Craig I McKenzie, Alexandra R Dvorscek, Zhoujie Ding, Marcus J Robinson, Kristy O'Donnell, Catherine Pitt, Daniel T Ferguson, Jesse Mulder, Marco J Herold, David M Tarlinton, Isaak Quast

{"title":"Syndecans and glycosaminoglycans influence B-cell development and activation.","authors":"Craig I McKenzie, Alexandra R Dvorscek, Zhoujie Ding, Marcus J Robinson, Kristy O'Donnell, Catherine Pitt, Daniel T Ferguson, Jesse Mulder, Marco J Herold, David M Tarlinton, Isaak Quast","doi":"10.1038/s44319-025-00432-6","DOIUrl":"10.1038/s44319-025-00432-6","url":null,"abstract":"Syndecans (SDCs) are glycosaminoglycan-containing cell surface proteins with diverse functions in the immune system with SDC1 (CD138) and SDC4 expressed in B-lineage cells. Here, we show that stem cells lacking either molecule generate fewer B-cell progenitors but give rise to mature B cells in vivo. Deletion of the plasma cell \"marker\" CD138 has no effect on homeostatic or antigen-induced plasma cell formation. Naive B cells express high SDC4 and encounter with cognate antigen results in transient CD138 upregulation and SDC4 loss, both further modulated by IL-4, IL-21, and CD40 ligation. SDC4 is downregulated on germinal center B cells and absent on most memory B cells. Glycosaminoglycans such as those attached to SDCs, and heparin, a commonly used therapeutic, regulate survival and activation of naive B cells by limiting responsiveness to cognate antigen. Conversely, ablation of SDC4 results in increased baseline and antigen-induced B-cell activation. Collectively, our data reveal B-cell activation- and subset-dependent SDC expression and show that SDC4 and GAGs can limit antigen-induced activation to promote B-cell survival and expansion.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Praja2 controls P-body assembly and translation in glioblastoma by non-proteolytic ubiquitylation of DDX6. Praja2通过DDX6的非蛋白水解泛素化控制胶质母细胞瘤中p体的组装和翻译。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-27 DOI: 10.1038/s44319-025-00425-5

Emanuela Senatore, Rosario Avolio, Laura Rinaldi, Francesco Chiuso, Maria A Oliva, Chiara D'Ambrosio, Antonio Giuseppe Bianco, Emiliano Dalla, Stefano Maria Pagnotta, Raffaella Flammia, Concetta Ambrosino, Domenico Memoli, Gabriele Turacchio, Sonia Ines Mimoune, Yves Toiron, Stephane Audebert, Luc Camoin, Luca Lignitto, Andrea Scaloni, Antonietta Arcella, Antonio Feliciello

{"title":"Praja2 controls P-body assembly and translation in glioblastoma by non-proteolytic ubiquitylation of DDX6.","authors":"Emanuela Senatore, Rosario Avolio, Laura Rinaldi, Francesco Chiuso, Maria A Oliva, Chiara D'Ambrosio, Antonio Giuseppe Bianco, Emiliano Dalla, Stefano Maria Pagnotta, Raffaella Flammia, Concetta Ambrosino, Domenico Memoli, Gabriele Turacchio, Sonia Ines Mimoune, Yves Toiron, Stephane Audebert, Luc Camoin, Luca Lignitto, Andrea Scaloni, Antonietta Arcella, Antonio Feliciello","doi":"10.1038/s44319-025-00425-5","DOIUrl":"10.1038/s44319-025-00425-5","url":null,"abstract":"Glioblastoma multiforme (GBM) is the most lethal form of malignant brain tumor in adults. Dysregulation of protein synthesis contributes to cancer cell plasticity, driving GBM cell heterogeneity, metastatic behavior, and drug resistance. Understanding the complex network and signaling pathways governing protein translation, is therefore an important goal for GBM treatment. Here we identify a novel signaling network centered on the E3 ubiquitin ligase praja2 that controls protein translation in GBM. Praja2 forms a multimeric complex with the RNA helicase DDX6, which inhibits translation of target RNAs within processing bodies (P-bodies). Stimulation of cAMP signaling through activation of G-protein-coupled receptors induces P-body assembly through praja2-mediated non-proteolytic polyubiquitylation of DDX6. Genetic inactivation of praja2 reshapes DDX6/mRNA complexes and translating polysomes and promotes cellular senescence and GBM growth arrest. Expression of an ubiquitylation-defective DDX6 mutant suppresses the assembly of P-bodies and sustains GBM growth. Taken together, our findings identify a cAMP-driven network that controls translation in P-bodies and GBM growth.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Gen AI and research integrity: Where to now? : The integration of Generative AI in the research process challenges well-established definitions of research integrity. 新一代人工智能与研究诚信：何去何从？生成式人工智能在研究过程中的整合挑战了研究完整性的既定定义。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-24 DOI: 10.1038/s44319-025-00424-6

Sonia Vasconcelos, Ana Marušić

引用次数: 0

Molecular architecture of glideosome and nuclear F-actin in Plasmodium falciparum. 恶性疟原虫滑体和核f -肌动蛋白的分子结构。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-24 DOI: 10.1038/s44319-025-00415-7

Vojtěch Pražák, Daven Vasishtan, Kay Grünewald, Ross G Douglas, Josie L Ferreira

{"title":"Molecular architecture of glideosome and nuclear F-actin in Plasmodium falciparum.","authors":"Vojtěch Pražák, Daven Vasishtan, Kay Grünewald, Ross G Douglas, Josie L Ferreira","doi":"10.1038/s44319-025-00415-7","DOIUrl":"https://doi.org/10.1038/s44319-025-00415-7","url":null,"abstract":"Actin-based motility is required for the transmission of malaria sporozoites. While this has been shown biochemically, filamentous actin has remained elusive and has not been directly visualised inside the parasite. Using focused ion beam milling and electron cryo-tomography, we studied dynamic actin filaments in unperturbed Plasmodium falciparum cells for the first time. This allowed us to dissect the assembly, path and fate of actin filaments during parasite gliding and determine a complete 3D model of F-actin within sporozoites. We observe micrometre long actin filaments, much longer than expected from in vitro studies. After their assembly at the parasite's apical end, actin filaments continue to grow as they are transported down the cell as part of the glideosome machinery, and are disassembled at the basal end in a rate-limiting step. Large pores in the IMC, constrained to the basal end, may facilitate actin exchange between the pellicular space and cytosol for recycling and maintenance of directional flow. The data also reveal striking actin bundles in the nucleus. Implications for motility and transmission are discussed.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Distinct pathogenic mutations in ARF1 allow dissection of its dual role in cGAS-STING signalling. ARF1中不同的致病突变允许解剖其在cGAS-STING信号传导中的双重作用。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-24 DOI: 10.1038/s44319-025-00423-7

Johannes Lang, Tim Bergner, Julia Zinngrebe, Alice Lepelley, Katharina Vill, Steffen Leiz, Meinhard Wlaschek, Matias Wagner, Karin Scharffetter-Kochanek, Pamela Fischer-Posovszky, Clarissa Read, Yanick J Crow, Maximilian Hirschenberger, Konstantin M J Sparrer

{"title":"Distinct pathogenic mutations in ARF1 allow dissection of its dual role in cGAS-STING signalling.","authors":"Johannes Lang, Tim Bergner, Julia Zinngrebe, Alice Lepelley, Katharina Vill, Steffen Leiz, Meinhard Wlaschek, Matias Wagner, Karin Scharffetter-Kochanek, Pamela Fischer-Posovszky, Clarissa Read, Yanick J Crow, Maximilian Hirschenberger, Konstantin M J Sparrer","doi":"10.1038/s44319-025-00423-7","DOIUrl":"10.1038/s44319-025-00423-7","url":null,"abstract":"Tight control of cGAS-STING-mediated DNA sensing is crucial to avoid auto-inflammation. The GTPase ADP-ribosylation factor 1 (ARF1) is crucial to maintain cGAS-STING homeostasis and various pathogenic ARF1 variants are associated with type I interferonopathies. Functional ARF1 inhibits STING activity by maintaining mitochondrial integrity and facilitating COPI-mediated retrograde STING trafficking and deactivation. Yet the factors governing the two distinct functions of ARF1 remained unexplored. Here, we dissect ARF1's dual role by a comparative analysis of disease-associated ARF1 variants and their impact on STING signalling. We identify a de novo heterozygous s.55 C > T/p.R19C ARF1 variant in a patient with type I interferonopathy symptoms. The GTPase-deficient variant ARF1 R19C selectively disrupts COPI binding and retrograde transport of STING, thereby prolonging innate immune activation without affecting mitochondrial integrity. Treatment of patient fibroblasts in vitro with the STING signalling inhibitors H-151 and amlexanox reduces chronic interferon signalling. Summarizing, our data reveal the molecular basis of a ARF1-associated type I interferonopathy allowing dissection of the two roles of ARF1, and suggest that pharmacological targeting of STING may alleviate ARF1-associated auto-inflammation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Induction of a transcriptional adaptation response by RNA destabilization events. RNA不稳定事件诱导的转录适应反应。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-24 DOI: 10.1038/s44319-025-00427-3

Lihan Xie, Gabrielius Jakutis, Christopher M Dooley, Stefan Guenther, Zacharias Kontarakis, Sarah P Howard, Thomas Juan, Didier Y R Stainier

{"title":"Induction of a transcriptional adaptation response by RNA destabilization events.","authors":"Lihan Xie, Gabrielius Jakutis, Christopher M Dooley, Stefan Guenther, Zacharias Kontarakis, Sarah P Howard, Thomas Juan, Didier Y R Stainier","doi":"10.1038/s44319-025-00427-3","DOIUrl":"10.1038/s44319-025-00427-3","url":null,"abstract":"Transcriptional adaptation (TA) is a cellular process whereby mRNA-destabilizing mutations are associated with the transcriptional upregulation of so-called adapting genes. The nature of the TA-triggering factor(s) remains unclear, namely whether an mRNA-borne premature termination codon or the subsequent mRNA decay process, and/or its products, elicits TA. Here, working with mouse Actg1, we first establish two types of perturbations that lead to mRNA destabilization: Cas9-induced mutations predicted to lead to mutant mRNA decay, and Cas13d-mediated mRNA cleavage. We find that both types of perturbations are effective in degrading Actg1 mRNA, and that they both upregulate Actg2. Notably, increased chromatin accessibility at the Actg2 locus was observed only in the Cas9-induced mutant cells but not in the Cas13d-targeted cells, suggesting that chromatin remodeling is not required for Actg2 upregulation. We further show that ribozyme-mediated Actg1 pre-mRNA cleavage also leads to a robust upregulation of Actg2, and that this upregulation is again independent of chromatin remodeling. Together, these data highlight the critical role of RNA destabilization events as a trigger for TA, or at least a TA-like response.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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