EMBO Reports最新文献_第9页

Identification of a fungal antibacterial endopeptidase that cleaves peptidoglycan. 分离肽聚糖的真菌抗菌内肽酶的鉴定。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-04 DOI: 10.1038/s44319-025-00508-3

Silke Machata, Ute Bertsche, Franziska Hoffmann, Zaher M Fattal, Franziska Kage, Michal Flak, Alexander N J Iliou, Falk Hillmann, Ferdinand von Eggeling, Hortense Slevogt, Axel A Brakhage, Ilse D Jacobsen

{"title":"Identification of a fungal antibacterial endopeptidase that cleaves peptidoglycan.","authors":"Silke Machata, Ute Bertsche, Franziska Hoffmann, Zaher M Fattal, Franziska Kage, Michal Flak, Alexander N J Iliou, Falk Hillmann, Ferdinand von Eggeling, Hortense Slevogt, Axel A Brakhage, Ilse D Jacobsen","doi":"10.1038/s44319-025-00508-3","DOIUrl":"10.1038/s44319-025-00508-3","url":null,"abstract":"Aspergillus fumigatus is a saprophytic fungus dwelling in soil and on decaying plant material, but also an opportunistic pathogen in immunocompromised patients. In its environmental niche, A. fumigatus faces competition from other microorganisms including bacteria. Here, we describe the discovery of the first secreted antibacterial protein in A. fumigatus. We identify a secreted fungal endopeptidase, designated CwhA, that cleaves peptidoglycan of Gram-positive bacteria at specific residues within the peptidoglycan stem peptide. Cleavage leads to bacterial lysis and the release of peptidoglycan cleavage products. Expression of cwhA is induced by the presence of bacteria. Furthermore, CwhA is highly abundant in murine lungs during invasive pulmonary aspergillosis and peptidoglycan cleavage products generated by CwhA stimulate cytokine production of human immune cells in vitro. Although CwhA does not affect human cells directly, this novel player in fungal-bacterial interactions could affect A. fumigatus infections by inhibiting Gram-positive bacteria in its vicinity, and possibly modulate the immune system.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3889-3916"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564692","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

NAT10-mediated acetylation of NIK mRNA in B cells promotes IgA production. nat10介导的B细胞NIK mRNA乙酰化促进了IgA的产生。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-04 DOI: 10.1038/s44319-025-00509-2

Wan-Jun Jiang, Xin-Tao Mao, Wen-Ping Li, Nicole Jin, Yu Wang, Guiping Guan, Jin Jin, Yi-Yuan Li

引用次数: 0

Immune aging impairs muscle regeneration via macrophage-derived anti-oxidant selenoprotein P. 免疫老化通过巨噬细胞来源的抗氧化硒蛋白P损害肌肉再生。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-18 DOI: 10.1038/s44319-025-00516-3

Dieu-Huong Hoang, Jessica Bouvière, Johanna Galvis, Pauline Moullé, Orane Mercier, Eugenia Migliavacca, Ananga Ghosh, Gaëtan Juban, Sophie Liot, Pascal Stuelsatz, Fabien Le Grand, Jérôme N Feige, Rémi Mounier, Bénédicte Chazaud

{"title":"Immune aging impairs muscle regeneration via macrophage-derived anti-oxidant selenoprotein P.","authors":"Dieu-Huong Hoang, Jessica Bouvière, Johanna Galvis, Pauline Moullé, Orane Mercier, Eugenia Migliavacca, Ananga Ghosh, Gaëtan Juban, Sophie Liot, Pascal Stuelsatz, Fabien Le Grand, Jérôme N Feige, Rémi Mounier, Bénédicte Chazaud","doi":"10.1038/s44319-025-00516-3","DOIUrl":"10.1038/s44319-025-00516-3","url":null,"abstract":"Muscle regeneration is impaired with aging, due to both intrinsic defects of muscle stem cells (MuSCs) and alterations of their niche. Here, we monitor the cells constituting the MuSC niche over time in young and old regenerating mouse muscle. Aging alters the expansion of all niche cells, with prominent phenotypes in macrophages that show impaired resolution of inflammation. RNA sequencing of FACS-isolated mononucleated cells uncovers specific profiles and kinetics of genes and molecular pathways in old versus young muscle cells, indicating that each cell type responds to aging in a specific manner. Moreover, we show that macrophages have an altered expression of Selenoprotein P (Sepp1). Macrophage-specific deletion of Sepp1 is sufficient to impair the acquisition of their restorative profile and causes inefficient skeletal muscle regeneration. When transplanted in aged mice, bone marrow from young WT mice, but not Sepp1-KOs, restores muscle regeneration. This work provides a unique resource to study MuSC niche aging, reveals that niche cell aging is asynchronous and establishes the antioxidant Selenoprotein P as a driver of age-related decline of muscle regeneration.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4153-4179"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667415","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

Student hostages in culture war. 文化战争中的学生人质。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-31 DOI: 10.1038/s44319-025-00527-0

Bernd Pulverer

引用次数: 0

Hippo pathway controls biopterin metabolism to shield adjacent cells from ferroptosis in lung cancer. Hippo通路控制生物蝶呤代谢以保护肺癌中邻近细胞免于铁下垂。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-07 DOI: 10.1038/s44319-025-00515-4

Hao Li, Yohei Kanamori, Akihiro Nita, Ayato Maeda, Tianli Zhang, Kenta Kikuchi, Hiroyuki Yamada, Touya Toyomoto, Mohamed Fathi Saleh, Mayumi Niimura, Hironori Hinokuma, Mayuko Shimoda, Koei Ikeda, Makoto Suzuki, Yoshihiro Komohara, Daisuke Kurotaki, Tomohiro Sawa, Toshiro Moroishi

{"title":"Hippo pathway controls biopterin metabolism to shield adjacent cells from ferroptosis in lung cancer.","authors":"Hao Li, Yohei Kanamori, Akihiro Nita, Ayato Maeda, Tianli Zhang, Kenta Kikuchi, Hiroyuki Yamada, Touya Toyomoto, Mohamed Fathi Saleh, Mayumi Niimura, Hironori Hinokuma, Mayuko Shimoda, Koei Ikeda, Makoto Suzuki, Yoshihiro Komohara, Daisuke Kurotaki, Tomohiro Sawa, Toshiro Moroishi","doi":"10.1038/s44319-025-00515-4","DOIUrl":"10.1038/s44319-025-00515-4","url":null,"abstract":"Recent advances in single-cell technologies have uncovered significant cellular diversity in tumors, influencing cancer progression and treatment outcomes. The Hippo pathway controls cell proliferation through its downstream effectors: yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ). Our analysis of human lung adenocarcinoma and murine models revealed that cancer cells display heterogeneous YAP/TAZ activation levels within tumors. Murine lung cancer cells with high YAP/TAZ activity grow rapidly but are sensitive to ferroptosis, a cell death induced by lipid peroxidation. In contrast, cells with low YAP/TAZ activity grow slowly but resist ferroptosis. Moreover, they protect neighbouring cells from ferroptosis, creating a protective microenvironment that enhances the tumor's resistance to ferroptosis. Mechanistically, inhibiting YAP/TAZ upregulates GTP cyclohydrolase 1 (GCH1), an enzyme critical for the biosynthesis of tetrahydrobiopterin (BH4), which functions as a secretory antioxidant to prevent lipid peroxidation. Pharmacological inhibition of GCH1 sensitizes lung cancer cells to ferroptosis inducers, suggesting a potential therapeutic approach. Our data highlights the non-cell-autonomous roles of the Hippo pathway in creating a ferroptosis-resistant tumor microenvironment.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4124-4152"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575075","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

Growth phase diets diminish histone acetyltransferase Gcn5 function and shorten lifespan of Drosophila males. 生长期饮食降低组蛋白乙酰转移酶Gcn5功能，缩短雄性果蝇寿命。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-10 DOI: 10.1038/s44319-025-00503-8

Shoko Mizutani, Kanji Furuya, Ayumi Mure, Yuuki Takahashi, Akihiro Mori, Nozomu Sakurai, Takuto Suito, Kohjiro Nagao, Masato Umeda, Kaori Watanabe, Yukako Hattori, Tadashi Uemura

{"title":"Growth phase diets diminish histone acetyltransferase Gcn5 function and shorten lifespan of Drosophila males.","authors":"Shoko Mizutani, Kanji Furuya, Ayumi Mure, Yuuki Takahashi, Akihiro Mori, Nozomu Sakurai, Takuto Suito, Kohjiro Nagao, Masato Umeda, Kaori Watanabe, Yukako Hattori, Tadashi Uemura","doi":"10.1038/s44319-025-00503-8","DOIUrl":"10.1038/s44319-025-00503-8","url":null,"abstract":"The nutritional environment in early life, referred to as the nutrition history, exerts far-reaching health effects beyond the developmental stage. Here, with Drosophila melanogaster as a model, we fed larvae on diets consisting of a variety of yeast mutants and explored the resulting histories that impacted adult lifespan. A larval diet comprised of yeast nat3 KO shortened the lifespan of male adults; and remarkably, this diet diminished the function of histone acetyltransferase Gcn5 in larvae. Concordantly, perturbation of Gcn5-mediated gene regulation in the larval whole body or neurons significantly contributed to the earlier death of adults. The nat3 KO diet is much more abundant in long-chain fatty acids and branched-chain amino acids (BCAAs) than the control yeast diet. Supplementing the control diet with a combination of oleic acid, valine, and acetic acid recapitulated the effects of the nat3 KO diet on the larval transcriptome and the lifespan of males. Our findings strongly suggest a causal link between a fatty acids- and BCAA-rich diet in developmental stages and lifespan reduction via the adverse effect on the Gcn5 function.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3856-3888"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607852","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

Palmitoylated importin α regulates mitotic spindle orientation through interaction with NuMA. 棕榈酰化输入蛋白α通过与NuMA相互作用调节有丝分裂纺锤体取向。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-05-27 DOI: 10.1038/s44319-025-00484-8

Patrick James Sutton, Natalie Mosqueda, Christopher W Brownlee

{"title":"Palmitoylated importin α regulates mitotic spindle orientation through interaction with NuMA.","authors":"Patrick James Sutton, Natalie Mosqueda, Christopher W Brownlee","doi":"10.1038/s44319-025-00484-8","DOIUrl":"10.1038/s44319-025-00484-8","url":null,"abstract":"Regulation of cell division orientation is a fundamental process critical to differentiation and tissue homeostasis. Microtubules emanating from the mitotic spindle pole bind a conserved complex of proteins at the cell cortex which orients the spindle and ultimately the cell division plane. Control of spindle orientation is of particular importance in developing tissues, such as the developing brain. Misorientation of the mitotic spindle and thus subsequent division plane misalignment can contribute to improper segregation of cell fate determinants in developing neuroblasts, leading to a rare neurological disorder known as microcephaly. We demonstrate that the nuclear transport protein importin α, when palmitoylated, plays a critical role in mitotic spindle orientation through localizing factors, such as NuMA, to the cell cortex. We also observe craniofacial developmental defects in Xenopus laevis when importin α palmitoylation is abrogated, including smaller head and brains, a hallmark of spindle misorientation and microcephaly. These findings characterize not only a role for importin α in spindle orientation, but also a broader role for importin α palmitoylation which has significance for many cellular processes.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3280-3304"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157325","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

Inflammation and IL-4 regulate Parkinson's and Crohn's disease associated kinase LRRK2. 炎症和IL-4调节帕金森病和克罗恩病相关激酶LRRK2。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-05-20 DOI: 10.1038/s44319-025-00473-x

Dina Dikovskaya, Rebecca Pemberton, Matthew Taylor, Anna Tasegian, Purbasha Bhattacharya, Karolina Zeneviciute, Esther M Sammler, Andrew J M Howden, Dario R Alessi, Mahima Swamy

{"title":"Inflammation and IL-4 regulate Parkinson's and Crohn's disease associated kinase LRRK2.","authors":"Dina Dikovskaya, Rebecca Pemberton, Matthew Taylor, Anna Tasegian, Purbasha Bhattacharya, Karolina Zeneviciute, Esther M Sammler, Andrew J M Howden, Dario R Alessi, Mahima Swamy","doi":"10.1038/s44319-025-00473-x","DOIUrl":"10.1038/s44319-025-00473-x","url":null,"abstract":"Mutations in Leucine-Rich Repeat protein Kinase 2 (LRRK2) are associated with Parkinson's disease (PD) and Crohn's disease (CD), but the regulation of LRRK2 during inflammation remains relatively unexplored. Here we describe the development of a flow cytometry-based assay to assess LRRK2 activity in individual cells and the generation of an EGFP-Lrrk2 knock-in reporter mouse to analyse cell-specific LRRK2 expression. Using these tools, we measured LRRK2 levels and activity in murine splenic and intestinal immune cells and in human blood. Anti-CD3 induced inflammation increases LRRK2 expression and activity in B cells and monocytes, while in mature neutrophils, inflammation stimulates activity but reduces LRRK2 expression. A kinase-activating PD-associated LRRK2-R1441C mutation exacerbates inflammation-induced activation of LRRK2 specifically in monocytes and macrophages. We identify IL-4 as a novel T-cell-derived factor that upregulates LRRK2 expression and activity in B cells, replicating inflammatory effects observed in vivo. Our findings provide valuable new insights into the regulation of the LRRK2 pathway in immune cells, crucial for understanding LRRK2 and its therapeutic potential in inflammatory diseases such as CD.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3327-3356"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109822","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

Author Correction: Biometrics' new identity-measuring more physical and biological traits. 作者更正：生物识别技术的新身份——测量更多的生理和生物特征。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 DOI: 10.1038/s44319-025-00506-5

Andrea Rinaldi

引用次数: 0

Laminin-defined mechanical status modulates retinal pigment epithelium phagocytosis. 层粘连蛋白定义的机械状态调节视网膜色素上皮吞噬。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-05-19 DOI: 10.1038/s44319-025-00475-9

Aleksandra N Kozyrina, Teodora Piskova, Francesca Semeraro, Iris C Doolaar, Taspia Prapty, Tamás Haraszti, Maxime Hubert, Reinhard Windoffer, Rudolf E Leube, Ana-Sunčana Smith, Jacopo Di Russo

{"title":"Laminin-defined mechanical status modulates retinal pigment epithelium phagocytosis.","authors":"Aleksandra N Kozyrina, Teodora Piskova, Francesca Semeraro, Iris C Doolaar, Taspia Prapty, Tamás Haraszti, Maxime Hubert, Reinhard Windoffer, Rudolf E Leube, Ana-Sunčana Smith, Jacopo Di Russo","doi":"10.1038/s44319-025-00475-9","DOIUrl":"10.1038/s44319-025-00475-9","url":null,"abstract":"Epithelial cells exhibit strong interconnections that are crucial for tissue mechanical properties. In homeostasis, these properties, termed mechanical homeostasis, depend on the balance between intercellular tension and extracellular matrix (ECM) adhesion forces. While age-related ECM remodeling is linked to outer retinal disease, its fundamental role in mechanical homeostasis remains unclear. In our study, we quantified changes in the mechanical state of retinal pigment epithelium (RPE), revealing a correlation with gradients of basement membrane laminins and their integrin receptors, β1 and β4. This relationship is related to regional phagocytic demand for recycling photoreceptor outer segments. Using a reductionist approach, we found that laminin 332 and laminin 511 isoforms differentially influence engagement with β1 and β4 integrins at low densities. Notably, laminin 511 enhances RPE contractility by reducing the β4 to β1 integrin engagement ratio, which subsequently diminishes phagocytic efficiency. Our findings suggest that the ECM-defined mechanical status of RPE serves as a novel parameter for visual function.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3357-3383"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101598","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