EMBO Reports最新文献_第9页

AML patient blasts exhibit polarization defects upon interaction with bone marrow stromal cells. AML患者原细胞在与骨髓基质细胞相互作用时表现出极化缺陷。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-06-11 DOI: 10.1038/s44319-025-00466-w

Khansa Saadallah, Benoît Vianay, Louise Bonnemay, Hélène Pasquer, Lois Kelly, Stéphanie Mathis, Cécile Culeux, Raphael Marie, Paul Arthur Meslin, Sofiane Fodil, Paul Chaintreuil, Emeline Kerreneur, Arnaud Jacquel, Emmanuel Raffoux, Rémy Nizard, Camille Lobry, Laurent Blanchoin, Lina Benajiba, Manuel Théry

{"title":"AML patient blasts exhibit polarization defects upon interaction with bone marrow stromal cells.","authors":"Khansa Saadallah, Benoît Vianay, Louise Bonnemay, Hélène Pasquer, Lois Kelly, Stéphanie Mathis, Cécile Culeux, Raphael Marie, Paul Arthur Meslin, Sofiane Fodil, Paul Chaintreuil, Emeline Kerreneur, Arnaud Jacquel, Emmanuel Raffoux, Rémy Nizard, Camille Lobry, Laurent Blanchoin, Lina Benajiba, Manuel Théry","doi":"10.1038/s44319-025-00466-w","DOIUrl":"10.1038/s44319-025-00466-w","url":null,"abstract":"Hematopoietic stem and progenitor cells (HSPCs) polarize in contact with the bone marrow stromal cells constituting their niche. Given the role of cell polarity in protection against tumorigenesis and the importance of the niche in the progression of acute myeloid leukemias (AMLs), we investigated the polarization capacities of leukemic blasts. Using engineered micro-niches and centrosome position with respect to the contact site with stromal cells as a proxy for cell polarization, we show that AML cell lines and primary cells from AML patient blasts are unable to polarize in contact with healthy stromal cells. Exposure to AML patient-derived stromal cells compromises the polarization of healthy adult HSPCs and AML blasts from patients. When cultured in \"bone-marrow-on-a-chip\", stromal cells from a leukemic niche stimulate the migration of healthy HSPCs and AML blast. These results reveal the detrimental influences of both intrinsic transformation and extrinsic contact with transformed stromal cells on the polarization of AML blasts.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3264-3279"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274433","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

Regulated microexon alternative splicing in single neurons tunes synaptic function. 单个神经元微外显子选择性剪接调节突触功能。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-06-09 DOI: 10.1038/s44319-025-00493-7

Bikash Choudhary, Rebekah Napier-Jameson, Adam Norris

{"title":"Regulated microexon alternative splicing in single neurons tunes synaptic function.","authors":"Bikash Choudhary, Rebekah Napier-Jameson, Adam Norris","doi":"10.1038/s44319-025-00493-7","DOIUrl":"10.1038/s44319-025-00493-7","url":null,"abstract":"Microexons are important components of the neuronal transcriptome. Though tiny, their splicing is essential for neuronal development and function. Microexons are typically included in the nervous system and skipped in other tissues, but less is known about whether they are alternatively spliced across neuron types, and if so what the regulatory mechanisms and functional consequences might be. We set out to globally address this question in C. elegans using deep single-cell transcriptomes and in vivo splicing reporters. We find widespread alternative microexon splicing across neuron types. Focusing on a broadly-conserved 9-nucleotide exon in the synaptic vesicle gene unc-13, we find that it is completely skipped in olfactory neurons, but completely included in motor neurons. This splicing pattern is established by two neuronal RNA binding proteins which recruit spliceosomal component PRP-40 to mediate microexon inclusion. Cell-specific microexon alternative splicing is functionally important, as forcing microexon inclusion causes olfactory defects, while forcing microexon skipping causes locomotory defects. These locomotory defects are caused by decreased inhibitory motor neuron synaptic transmission and altered synaptic vesicle distribution. Regulatory features of unc-13 microexon splicing are broadly conserved: related MUN-domain genes in worms, flies, and mice invariably encode microexons, and those we tested are subject to similar regulatory principles (e.g. included in motor neurons, skipped in olfactory neurons, and regulated by the same two RNA binding proteins). Thus, not only is microexon inclusion important for nervous system function, but microexon alternative splicing across neurons is important for tuning neuronal function in individual cell types.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3640-3662"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257583","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

Mental privacy: navigating risks, rights and regulation : Advances in neuroscience challenge contemporary legal frameworks to protect mental privacy. 精神隐私：驾驭风险、权利和监管：神经科学的进步挑战了当代保护精神隐私的法律框架。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-06-25 DOI: 10.1038/s44319-025-00505-6

Łukasz Szoszkiewicz, Rafael Yuste

引用次数: 0

BZR1 promotes pluripotency acquisition and callus development through direct regulation of ARF7 and ARF19. BZR1通过直接调控ARF7和ARF19促进多能性获得和愈伤组织发育。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-06-26 DOI: 10.1038/s44319-025-00433-5

Thomas Ammitsøe, Elise Ebstrup, Noel Blanco-Touriñán, Julie Hansen, Christian S Hardtke, Morten Petersen, Eleazar Rodriguez

{"title":"BZR1 promotes pluripotency acquisition and callus development through direct regulation of ARF7 and ARF19.","authors":"Thomas Ammitsøe, Elise Ebstrup, Noel Blanco-Touriñán, Julie Hansen, Christian S Hardtke, Morten Petersen, Eleazar Rodriguez","doi":"10.1038/s44319-025-00433-5","DOIUrl":"10.1038/s44319-025-00433-5","url":null,"abstract":"Plants have the remarkable ability to regenerate whole organisms through the formation of pluripotent cell masses from somatic cells. Cellular programs leading to fate change resemble lateral root (LR) formation and are chiefly regulated by auxin. Brassinosteroid signaling also plays an important role in LR formation, but little is known about the direct link between auxin and brassinosteroid components, such as BZR1 and BES1, in pluripotency acquisition. Here we show that gain-of-function mutants bzr1-D and bes1-D exhibit altered callus formation, yet disruption of these transcription factors does not cause major changes to callus formation or de novo organogenesis. Moreover, our data reveal that BZR1 displays enhanced expression in callus tissue and directly binds to the promoters of ARF7 and ARF19, two master pluripotency regulators, leading to their enhanced transcription. Remarkably, callus formation is abrogated in bzr1-D upon disruption of these ARFs, emphasizing that the callus formation via BZR1 depends on these auxin signaling components. In conclusion, we depict a link between, ARF7, ARF19, and BZR1 in promoting pluripotency acquisition, portraying BZR1 as a major supporting factor in callus formation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3554-3573"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505132","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

LRRK2 interactions with microtubules are independent of LRRK2-mediated Rab phosphorylation. LRRK2与微管的相互作用不依赖于LRRK2介导的Rab磷酸化。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-05-27 DOI: 10.1038/s44319-025-00486-6

Tuyana Malankhanova, Zhiyong Liu, Enquan Xu, Nicole Bryant, Ki Woon Sung, Huizhong Li, Samuel Strader, Andrew B West

{"title":"LRRK2 interactions with microtubules are independent of LRRK2-mediated Rab phosphorylation.","authors":"Tuyana Malankhanova, Zhiyong Liu, Enquan Xu, Nicole Bryant, Ki Woon Sung, Huizhong Li, Samuel Strader, Andrew B West","doi":"10.1038/s44319-025-00486-6","DOIUrl":"10.1038/s44319-025-00486-6","url":null,"abstract":"Deregulated microtubules are common defects associated with neurodegenerative diseases. Recent cryo-electron microscopy studies in cell lines overexpressing Parkinson's disease-associated LRRK2 suggest microtubule surfaces may regulate kinase activity by stabilizing different LRRK2 conformations. In macrophages with high endogenous LRRK2 expression, we find that nocodazole treatment destabilizes microtubules and impairs LRRK2-mediated Rab phosphorylation. GTP supplementation restores nocodazole-reduced Rab phosphorylation, linking LRRK2 kinase action to cellular GTP levels. Chemical microtubule stabilization, and kinetically trapping LRRK2 to microtubule surfaces, has negligible effects on Rab phosphorylation. In contrast, trapping LRRK2 to LAMP1-positive membranes upregulates LRRK2-mediated Rab phosphorylation. Proximity-labeling proteomics and colocalization studies show that LRRK2 robustly interacts with both polymerized and free tubulin transiently and independently of LRRK2 kinase activity. Endogenous LRRK2 complexed with type I inhibitors in neurons and macrophages fails to stably interact with microtubules, whereas bulky N-terminal tags fused to LRRK2 promotes stable microtubule binding in cell lines. Collectively, these results show that tubulin isoforms and microtubules are transient LRRK2-interacting proteins non-essential for LRRK2-mediated Rab phosphorylation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3445-3466"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157323","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

Humour uncovers the wide landscape of life : From laughter to freedom. 幽默揭示了生活的广阔前景：从欢笑到自由。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-06-03 DOI: 10.1038/s44319-025-00494-6

Vladimir Leksa

引用次数: 0

DSK2-mediated degradation of F-box protein LAO1 and class I TCPs modulates the nitrogen starvation response. dsk2介导的F-box蛋白la1和I类tcp的降解调节氮饥饿反应。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-05-30 DOI: 10.1038/s44319-025-00491-9

Yuanyuan Li, Shuyang Cheng, Xu Jin, Ruoxuan Wu, Yiyi Guo, Dezhi Wu, Jie Dong

{"title":"DSK2-mediated degradation of F-box protein LAO1 and class I TCPs modulates the nitrogen starvation response.","authors":"Yuanyuan Li, Shuyang Cheng, Xu Jin, Ruoxuan Wu, Yiyi Guo, Dezhi Wu, Jie Dong","doi":"10.1038/s44319-025-00491-9","DOIUrl":"10.1038/s44319-025-00491-9","url":null,"abstract":"Plants have evolved intricate strategies to cope with various abiotic stresses. Ubiquitin-mediated protein degradation plays a key role in plant development as well as abiotic stress tolerance. In this study, we identify LAO1, an F-box protein with unknown function, as a negative regulator of plant fitness during nitrogen starvation. DOMINANT SUPPRESSOR OF KAR 2 (DSK2) interacts with and mediates the autophagic degradation of LAO1 protein during nitrogen starvation. The loss of LAO1 improves the fitness of an autophagy-deficient mutant, atg5-1, under nitrogen starvation. Intriguingly, mutations in DSK2 facilitate rather than reduce plant growth after nitrogen starvation. This unexpected effect of DSK2 knockout led us to discover that DSK2 also interacts with and degrades a group of class I TCP transcription factors. Phenotypic observations demonstrate that class I TCPs are crucial for plant adaptation to nitrogen starvation. Moreover, genetic analyses indicate that class I TCPs function downstream of LAO1 and counteract its negative effects. Collectively, our findings unveil a previously undescribed regulatory network governing plant fitness during nitrogen starvation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3614-3639"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186773","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

Regulated localization of transposable element RNA during influenza A virus infection. 甲型流感病毒感染期间转座因子RNA的调控定位。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-06-16 DOI: 10.1038/s44319-025-00498-2

Marie Lork, Liam Childs, Gauthier Lieber, Florence Kwaschik, Renate König, Benjamin G Hale

{"title":"Regulated localization of transposable element RNA during influenza A virus infection.","authors":"Marie Lork, Liam Childs, Gauthier Lieber, Florence Kwaschik, Renate König, Benjamin G Hale","doi":"10.1038/s44319-025-00498-2","DOIUrl":"10.1038/s44319-025-00498-2","url":null,"abstract":"Influenza A virus (IAV) infection triggers derepression of host transposable elements (TEs), which have the potential to form double-stranded (ds)RNAs and could enhance innate antiviral immunity. However, the contribution of TEs to stimulating such pathways during infection is unknown, and it remains unclear whether derepressed TEs actually form dsRNAs. Here, we perform strand-specific total RNA-Seq on nucleus-associated and cytosolic fractions from cells infected with wild-type IAV or an engineered IAV lacking NS1, a dsRNA-binding interferon-antagonist protein. Both infections globally increase levels of host TE RNAs with bioinformatic and experimental evidence for double-strandedness. However, NS1-deficient IAV leads to significantly more of these putative dsRNA-forming TEs accumulating in the cytosolic fraction. Co-precipitations identify that wild-type NS1, but not a dsRNA-binding mutant, associates with these TEs, and microscopy shows co-localization of wild-type NS1 with dsRNA in perinuclear regions. Our data reveal the double-stranded nature of some IAV-triggered host TEs and suggest that NS1-mediated sequestration could limit their engagement of cytosolic innate immune sensors.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3506-3528"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309715","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

ATR promotes mTORC1 activity via de novo cholesterol synthesis. ATR通过从头胆固醇合成促进mTORC1活性。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-06-13 DOI: 10.1038/s44319-025-00451-3

Naveen Kumar Tangudu, Alexandra N Grumet, Richard Fang, Raquel Buj, Aidan R Cole, Apoorva Uboveja, Amandine Amalric, Baixue Yang, Zhentai Huang, Cassandra Happe, Mai Sun, Stacy L Gelhaus, Matthew L MacDonald, Nadine Hempel, Nathaniel W Snyder, Katarzyna M Kedziora, Alexander J Valvezan, Katherine M Aird

{"title":"ATR promotes mTORC1 activity via de novo cholesterol synthesis.","authors":"Naveen Kumar Tangudu, Alexandra N Grumet, Richard Fang, Raquel Buj, Aidan R Cole, Apoorva Uboveja, Amandine Amalric, Baixue Yang, Zhentai Huang, Cassandra Happe, Mai Sun, Stacy L Gelhaus, Matthew L MacDonald, Nadine Hempel, Nathaniel W Snyder, Katarzyna M Kedziora, Alexander J Valvezan, Katherine M Aird","doi":"10.1038/s44319-025-00451-3","DOIUrl":"10.1038/s44319-025-00451-3","url":null,"abstract":"DNA damage and cellular metabolism exhibit a complex interplay characterized by bidirectional feedback. Key mediators of these pathways include ATR and mTORC1, respectively. Previous studies established ATR as a regulatory upstream factor of mTORC1 during replication stress; however, the precise mechanisms remain poorly defined. Additionally, the activity of this signaling axis in unperturbed cells has not been extensively investigated. We demonstrate that ATR promotes mTORC1 activity across various human cancer cells and both human and mouse normal cells under basal conditions. This effect is enhanced in human cancer cells (SKMEL28, RPMI-7951, HeLa) following knockdown of p16, a cell cycle inhibitor that we have previously found increases mTORC1 activity and here found increases ATR activity. Mechanistically, ATR promotes de novo cholesterol synthesis and mTORC1 activation through the phosphorylation and upregulation of lanosterol synthase (LSS), independently of both CHK1 and the TSC complex. Interestingly, this pathway is distinct from the regulation of mTORC1 by ATM and may be specific to cancer cells. Finally, ATR-mediated increased cholesterol correlates with enhanced localization of mTOR to lysosomes. Collectively, our findings demonstrate a novel connection linking ATR and mTORC1 signaling through the modulation of cholesterol metabolism.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3574-3593"},"PeriodicalIF":6.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293546","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 conserved phage phosphoesterase enables evasion of bacterial antiviral immunity. 一种保守的噬菌体磷酸酯酶可以逃避细菌抗病毒免疫。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-05-29 DOI: 10.1038/s44319-025-00488-4

Junlong Li, Yihao Song, Xiao Guo, Zheng-Guo He

{"title":"A conserved phage phosphoesterase enables evasion of bacterial antiviral immunity.","authors":"Junlong Li, Yihao Song, Xiao Guo, Zheng-Guo He","doi":"10.1038/s44319-025-00488-4","DOIUrl":"10.1038/s44319-025-00488-4","url":null,"abstract":"With the increasing prevalence of drug-resistant bacteria, antimicrobial resistance emerges as a global public health threat. Mycobacteriophages show exciting prospects for the treatment of drug-resistant bacterial infections. However, the molecular mechanism through which they escape host bacterial defenses remains unclear. Here, we report that the gene gp48 of the mycobacteriophage A10ZJ24, which encodes a metallophosphoesterase-like protein, is essential for killing Mycobacterium tuberculosis. Gp48 is expressed during early stages of phage infection, and the Gp48 protein efficiently disrupts mycobacterial genomic DNA integrity, thereby silencing the expression of multiple anti-phage defense genes. While gp48-deletion phages infect and inject their DNA normally into M. tuberculosis cells, they are not able to impair the activation of the bacterial anti-phage genes which inhibit the replication of the genomic DNA of the mutant phage. This study thus identifies a phage metallophosphoesterase as a novel tool for subverting host bacterial antiviral immunity and killing M. tuberculosis. Our work fills a critical gap in the current knowledge on the arms race between mycobacteriophages and M. tuberculosis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3594-3613"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180213","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