The EMBO Journal最新文献

Decitabine cytotoxicity is promoted by dCMP deaminase DCTD and mitigated by SUMO-dependent E3 ligase TOPORS. dCMP脱氨酶DCTD促进了地西他滨的细胞毒性，而依赖于SUMO的E3连接酶TOPORS则减轻了这种毒性。

The EMBO Journal Pub Date : 2024-05-17 DOI: 10.1038/s44318-024-00108-2

Christopher J. Carnie, Maximilian J. Götz, Chloe S. Palma-Chaundler, P. Weickert, Amy R. Wanders, Almudena Serrano-Benitez, Hao-Yi Li, Vipul Gupta, Samah W Awwad, Christian J Blum, Matylda Sczaniecka-Clift, Jacqueline Cordes, Guido Zagnoli-Vieira, Giuseppina D'Alessandro, Sean L Richards, Nadia Gueorguieva, Simon Lam, Petra Beli, Julian Stingele, S. P. Jackson

引用次数: 0

Spatially distinct epithelial and mesenchymal cell subsets along progressive lineage restriction in the branching embryonic mammary gland. 在胚胎乳腺分支中，上皮细胞和间质细胞亚群在空间上沿着渐进的系谱限制而截然不同。

The EMBO Journal Pub Date : 2024-05-17 DOI: 10.1038/s44318-024-00115-3

Claudia Carabaña, Wenjie Sun, Camila Veludo Ramos, M. Huyghe, Meghan Perkins, Aurélien Maillot, Robin Journot, Fatima Hartani, Marisa M. Faraldo, B. Lloyd-Lewis, Silvia Fre

引用次数: 0

Receptor-mediated cargo hitchhiking on bulk autophagy. 受体介导的大量自噬货物搭便车。

The EMBO Journal Pub Date : 2024-05-16 DOI: 10.1038/s44318-024-00091-8

Eigo Takeda, Takahiro Isoda, Sachiko Hosokawa, Y. Oikawa, Shukun Hotta-Ren, Alexander I. May, Yoshinori Ohsumi

引用次数: 0

Early-stage lung cancer is driven by a transitional cell state dependent on a KRAS-ITGA3-SRC axis. 早期肺癌是由依赖于 KRAS-ITGA3-SRC 轴的过渡细胞状态驱动的。

The EMBO Journal Pub Date : 2024-05-16 DOI: 10.1038/s44318-024-00113-5

Aaron L. Moye, A. Dost, Robert Ietswaart, Shreoshi Sengupta, VanNashlee Ya, Chrystal Aluya, Caroline G. Fahey, S. M. Louie, Margherita Paschini, Carla F. Kim

引用次数: 0

Synergistic prostaglandin E synthesis by myeloid and endothelial cells promotes fetal hematopoietic stem cell expansion in vertebrates. 髓细胞和内皮细胞协同合成前列腺素E促进脊椎动物胎儿造血干细胞扩增。

IF 11.4

The EMBO Journal Pub Date : 2022-10-04 Epub Date: 2022-08-04 DOI: 10.15252/embj.2021108536

Pietro Cacialli, Marie-Pierre Mailhe, Ingrid Wagner, Doron Merkler, Rachel Golub, Julien Y Bertrand

{"title":"Synergistic prostaglandin E synthesis by myeloid and endothelial cells promotes fetal hematopoietic stem cell expansion in vertebrates.","authors":"Pietro Cacialli, Marie-Pierre Mailhe, Ingrid Wagner, Doron Merkler, Rachel Golub, Julien Y Bertrand","doi":"10.15252/embj.2021108536","DOIUrl":"https://doi.org/10.15252/embj.2021108536","url":null,"abstract":"During development, hematopoietic stem cells (HSCs) are produced from the hemogenic endothelium and will expand in a transient hematopoietic niche. Prostaglandin E2 (PGE2) is essential during vertebrate development and HSC specification, but its precise source in the embryo remains elusive. Here, we show that in the zebrafish embryo, PGE2 synthesis genes are expressed by distinct stromal cell populations, myeloid (neutrophils, macrophages), and endothelial cells of the caudal hematopoietic tissue. Ablation of myeloid cells, which produce the PGE2 precursor prostaglandin H2 (PGH2), results in loss of HSCs in the caudal hematopoietic tissue, which could be rescued by exogeneous PGE2 or PGH2 supplementation. Endothelial cells contribute by expressing the PGH2 import transporter slco2b1 and ptges3, the enzyme converting PGH2 into PGE2. Of note, differential niche cell expression of PGE2 biosynthesis enzymes is also observed in the mouse fetal liver. Taken altogether, our data suggest that the triad composed of neutrophils, macrophages, and endothelial cells sequentially and synergistically contributes to blood stem cell expansion during vertebrate development.","PeriodicalId":305851,"journal":{"name":"The EMBO Journal","volume":" ","pages":"e108536"},"PeriodicalIF":11.4,"publicationDate":"2022-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Endosome maturation links PI3Kα signaling to lysosome repopulation during basal autophagy. 核内体成熟将PI3Kα信号与基础自噬过程中的溶酶体再生联系起来。

IF 11.4

The EMBO Journal Pub Date : 2022-10-04 Epub Date: 2022-08-15 DOI: 10.15252/embj.2021110398

Samuel J Rodgers, Emily I Jones, Senthil Arumugam, Sabryn A Hamila, Jill Danne, Rajendra Gurung, Matthew J Eramo, Randini Nanayakkara, Georg Ramm, Meagan J McGrath, Christina A Mitchell

{"title":"Endosome maturation links PI3Kα signaling to lysosome repopulation during basal autophagy.","authors":"Samuel J Rodgers, Emily I Jones, Senthil Arumugam, Sabryn A Hamila, Jill Danne, Rajendra Gurung, Matthew J Eramo, Randini Nanayakkara, Georg Ramm, Meagan J McGrath, Christina A Mitchell","doi":"10.15252/embj.2021110398","DOIUrl":"https://doi.org/10.15252/embj.2021110398","url":null,"abstract":"Autophagy depends on the repopulation of lysosomes to degrade intracellular components and recycle nutrients. How cells co-ordinate lysosome repopulation during basal autophagy, which occurs constitutively under nutrient-rich conditions, is unknown. Here, we identify an endosome-dependent phosphoinositide pathway that links PI3Kα signaling to lysosome repopulation during basal autophagy. We show that PI3Kα-derived PI(3)P generated by INPP4B on late endosomes was required for basal but not starvation-induced autophagic degradation. PI(3)P signals were maintained as late endosomes matured into endolysosomes, and served as the substrate for the 5-kinase, PIKfyve, to generate PI(3,5)P2 . The SNX-BAR protein, SNX2, was recruited to endolysosomes by PI(3,5)P2 and promoted lysosome reformation. Inhibition of INPP4B/PIKfyve-dependent lysosome reformation reduced autophagic clearance of protein aggregates during proteotoxic stress leading to increased cytotoxicity. Therefore under nutrient-rich conditions, PI3Kα, INPP4B, and PIKfyve sequentially contribute to basal autophagic degradation and protection from proteotoxic stress via PI(3,5)P2 -dependent lysosome reformation from endolysosomes. These findings reveal that endosome maturation couples PI3Kα signaling to lysosome reformation during basal autophagy.","PeriodicalId":305851,"journal":{"name":"The EMBO Journal","volume":" ","pages":"e110398"},"PeriodicalIF":11.4,"publicationDate":"2022-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40698514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Single-molecule imaging reveals Tau trapping at nanometer-sized dynamic hot spots near the plasma membrane that persists after microtubule perturbation and cholesterol depletion. 单分子成像显示，在微管扰动和胆固醇消耗后，Tau蛋白在质膜附近的纳米级动态热点处被捕获。

IF 11.4

The EMBO Journal Pub Date : 2022-10-04 Epub Date: 2022-08-25 DOI: 10.15252/embj.2022111265

Pranesh Padmanabhan, Andrew Kneynsberg, Esteban Cruz, Rumelo Amor, Jean-Baptiste Sibarita, Jürgen Götz

{"title":"Single-molecule imaging reveals Tau trapping at nanometer-sized dynamic hot spots near the plasma membrane that persists after microtubule perturbation and cholesterol depletion.","authors":"Pranesh Padmanabhan, Andrew Kneynsberg, Esteban Cruz, Rumelo Amor, Jean-Baptiste Sibarita, Jürgen Götz","doi":"10.15252/embj.2022111265","DOIUrl":"https://doi.org/10.15252/embj.2022111265","url":null,"abstract":"Accumulation of aggregates of the microtubule-binding protein Tau is a pathological hallmark of Alzheimer's disease. While Tau is thought to primarily associate with microtubules, it also interacts with and localizes to the plasma membrane. However, little is known about how Tau behaves and organizes at the plasma membrane of live cells. Using quantitative, single-molecule imaging, we show that Tau exhibits spatial and kinetic heterogeneity near the plasma membrane of live cells, resulting in the formation of nanometer-sized hot spots. The hot spots lasted tens of seconds, much longer than the short dwell time (∼ 40 ms) of Tau on microtubules. Pharmacological and biochemical disruption of Tau/microtubule interactions did not prevent hot spot formation, suggesting that these are different from the reported Tau condensation on microtubules. Although cholesterol removal has been shown to reduce Tau pathology, its acute depletion did not affect Tau hot spot dynamics. Our study identifies an intrinsic dynamic property of Tau near the plasma membrane that may facilitate the formation of assembly sites for Tau to assume its physiological and pathological functions.","PeriodicalId":305851,"journal":{"name":"The EMBO Journal","volume":" ","pages":"e111265"},"PeriodicalIF":11.4,"publicationDate":"2022-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c9/91/EMBJ-41-e111265.PMC9531302.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40440531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Vaginal bacterium Prevotella timonensis turns protective Langerhans cells into HIV-1 reservoirs for virus dissemination. 阴道普雷沃氏菌将保护性朗格汉斯细胞转化为HIV-1病毒传播库。

IF 11.4

The EMBO Journal Pub Date : 2022-10-04 Epub Date: 2022-08-15 DOI: 10.15252/embj.2022110629

Nienke H van Teijlingen, Leanne C Helgers, Ramin Sarrami-Forooshani, Esther M Zijlstra-Willems, John L van Hamme, Celia Segui-Perez, Marleen Y van Smoorenburg, Hanneke Borgdorff, Janneke Hhm van de Wijgert, Elisabeth van Leeuwen, Joris Am van der Post, Karin Strijbis, Carla Ms Ribeiro, Teunis Bh Geijtenbeek

{"title":"Vaginal bacterium Prevotella timonensis turns protective Langerhans cells into HIV-1 reservoirs for virus dissemination.","authors":"Nienke H van Teijlingen, Leanne C Helgers, Ramin Sarrami-Forooshani, Esther M Zijlstra-Willems, John L van Hamme, Celia Segui-Perez, Marleen Y van Smoorenburg, Hanneke Borgdorff, Janneke Hhm van de Wijgert, Elisabeth van Leeuwen, Joris Am van der Post, Karin Strijbis, Carla Ms Ribeiro, Teunis Bh Geijtenbeek","doi":"10.15252/embj.2022110629","DOIUrl":"https://doi.org/10.15252/embj.2022110629","url":null,"abstract":"Dysbiosis of vaginal microbiota is associated with increased HIV-1 acquisition, but the underlying cellular mechanisms remain unclear. Vaginal Langerhans cells (LCs) protect against mucosal HIV-1 infection via autophagy-mediated degradation of HIV-1. As LCs are in continuous contact with bacterial members of the vaginal microbiome, we investigated the impact of commensal and dysbiosis-associated vaginal (an)aerobic bacterial species on the antiviral function of LCs. Most of the tested bacteria did not affect the HIV-1 restrictive function of LCs. However, Prevotella timonensis induced a vast uptake of HIV-1 by vaginal LCs. Internalized virus remained infectious for days and uptake was unaffected by antiretroviral drugs. P. timonensis-exposed LCs efficiently transmitted HIV-1 to target cells both in vitro and ex vivo. Additionally, P. timonensis exposure enhanced uptake and transmission of the HIV-1 variants that establish infection after sexual transmission, the so-called Transmitted Founder variants. Our findings, therefore, suggest that P. timonensis might set the stage for enhanced HIV-1 susceptibility during vaginal dysbiosis and advocate targeted treatment of P. timonensis during bacterial vaginosis to limit HIV-1 infection.","PeriodicalId":305851,"journal":{"name":"The EMBO Journal","volume":" ","pages":"e110629"},"PeriodicalIF":11.4,"publicationDate":"2022-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/30/44/EMBJ-41-e110629.PMC9531304.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40415653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Mammalian adipogenesis regulator (Areg) cells use retinoic acid signalling to be non- and anti-adipogenic in age-dependent manner. 哺乳动物脂肪生成调节细胞(Areg)使用视黄酸信号以年龄依赖的方式非和抗脂肪生成。

IF 11.4

The EMBO Journal Pub Date : 2022-09-15 Epub Date: 2022-08-22 DOI: 10.15252/embj.2021108206

Magda Zachara, Pernille Y Rainer, Horia Hashimi, Julie M Russeil, Daniel Alpern, Radiana Ferrero, Maria Litovchenko, Bart Deplancke

{"title":"Mammalian adipogenesis regulator (Areg) cells use retinoic acid signalling to be non- and anti-adipogenic in age-dependent manner.","authors":"Magda Zachara, Pernille Y Rainer, Horia Hashimi, Julie M Russeil, Daniel Alpern, Radiana Ferrero, Maria Litovchenko, Bart Deplancke","doi":"10.15252/embj.2021108206","DOIUrl":"https://doi.org/10.15252/embj.2021108206","url":null,"abstract":"Adipose stem and precursor cells (ASPCs) give rise to adipocytes and determine the composition and plasticity of adipose tissue. Recently, several studies have demonstrated that ASPCs partition into at least three distinct cell subpopulations, including the enigmatic CD142+ cells. An outstanding challenge is to functionally characterise this population, as discrepant properties, from adipogenic to non- and anti-adipogenic, have been reported for these cells. To resolve these phenotypic ambiguities, we characterised mammalian subcutaneous CD142+ ASPCs across various experimental conditions, demonstrating that CD142+ ASPCs exhibit high molecular and phenotypic robustness. Specifically, we find these cells to be firmly non- and anti-adipogenic both in vitro and in vivo, with their inhibitory signals also impacting adipogenic human cells. However, these CD142+ ASPC-specific properties exhibit surprising temporal phenotypic alterations, and emerge only in an age-dependent manner. Finally, using multi-omic and functional assays, we show that the inhibitory nature of these adipogenesis-regulatory CD142+ ASPCs (Aregs) is driven by specifically expressed secretory factors that cooperate with the retinoic acid signalling pathway to transform the adipogenic state of CD142- ASPCs into a non-adipogenic, Areg-like state.","PeriodicalId":305851,"journal":{"name":"The EMBO Journal","volume":" ","pages":"e108206"},"PeriodicalIF":11.4,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/15/ba/EMBJ-41-e108206.PMC9475530.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40633140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Barley GRIK1-SnRK1 kinases subvert a viral virulence protein to upregulate antiviral RNAi and inhibit infection. 大麦GRIK1-SnRK1激酶破坏病毒毒力蛋白，上调抗病毒RNAi并抑制感染。

IF 11.4

The EMBO Journal Pub Date : 2022-09-15 Epub Date: 2022-08-05 DOI: 10.15252/embj.2021110521

Huaibing Jin, Xinyun Han, Zhaohui Wang, Yilin Xie, Kunpu Zhang, Xiaoge Zhao, Lina Wang, Jin Yang, Huiyun Liu, Xiang Ji, Lingli Dong, Hongyuan Zheng, Weijuan Hu, Yan Liu, Xifeng Wang, Xueping Zhou, Yijing Zhang, Weiqiang Qian, Wenming Zheng, Qianhua Shen, Mingyue Gou, Daowen Wang

{"title":"Barley GRIK1-SnRK1 kinases subvert a viral virulence protein to upregulate antiviral RNAi and inhibit infection.","authors":"Huaibing Jin, Xinyun Han, Zhaohui Wang, Yilin Xie, Kunpu Zhang, Xiaoge Zhao, Lina Wang, Jin Yang, Huiyun Liu, Xiang Ji, Lingli Dong, Hongyuan Zheng, Weijuan Hu, Yan Liu, Xifeng Wang, Xueping Zhou, Yijing Zhang, Weiqiang Qian, Wenming Zheng, Qianhua Shen, Mingyue Gou, Daowen Wang","doi":"10.15252/embj.2021110521","DOIUrl":"https://doi.org/10.15252/embj.2021110521","url":null,"abstract":"Viruses often usurp host machineries for their amplification, but it remains unclear if hosts may subvert virus proteins to regulate viral proliferation. Here, we show that the 17K protein, an important virulence factor conserved in barley yellow dwarf viruses (BYDVs) and related poleroviruses, is phosphorylated by host GRIK1-SnRK1 kinases, with the phosphorylated 17K (P17K) capable of enhancing the abundance of virus-derived small interfering RNAs (vsiRNAs) and thus antiviral RNAi. Furthermore, P17K interacts with barley small RNA-degrading nuclease 1 (HvSDN1) and impedes HvSDN1-catalyzed vsiRNA degradation. Additionally, P17K weakens the HvSDN1-HvAGO1 interaction, thus hindering HvSDN1 from accessing and degrading HvAGO1-carried vsiRNAs. Importantly, transgenic expression of 17K phosphomimetics (17K5D ), or genome editing of SDN1, generates stable resistance to BYDV through elevating vsiRNA abundance. These data validate a novel mechanism that enhances antiviral RNAi through host subversion of a viral virulence protein to inhibit SDN1-catalyzed vsiRNA degradation and suggest new ways for engineering BYDV-resistant crops.","PeriodicalId":305851,"journal":{"name":"The EMBO Journal","volume":" ","pages":"e110521"},"PeriodicalIF":11.4,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/60/61/EMBJ-41-e110521.PMC9475517.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40683301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4