EMBO Journal最新文献

Author Correction: The barley MLA13-AVR_A13 heterodimer reveals principles for immunoreceptor recognition of RNase-like powdery mildew effectors. 作者更正：大麦MLA13-AVRA13异源二聚体揭示了rase样白粉病效应物的免疫受体识别原理。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-07 DOI: 10.1038/s44318-025-00456-7

Aaron W Lawson, Andrea Flores-Ibarra, Yu Cao, Chunpeng An, Ulla Neumann, Monika Gunkel, Isabel M L Saur, Jijie Chai, Elmar Behrmann, Paul Schulze-Lefert

引用次数: 0

Surface-mediated bacteriophage defense incurs fitness tradeoffs for interbacterial antagonism. 表面介导的噬菌体防御导致细菌间拮抗的适应性权衡。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-03-10 DOI: 10.1038/s44318-025-00406-3

Chia-En Tsai, Feng-Qi Wang, Chih-Wen Yang, Ling-Li Yang, Thao Vp Nguyen, Yung-Chih Chen, Po-Yin Chen, Ing-Shouh Hwang, See-Yeun Ting

{"title":"Surface-mediated bacteriophage defense incurs fitness tradeoffs for interbacterial antagonism.","authors":"Chia-En Tsai, Feng-Qi Wang, Chih-Wen Yang, Ling-Li Yang, Thao Vp Nguyen, Yung-Chih Chen, Po-Yin Chen, Ing-Shouh Hwang, See-Yeun Ting","doi":"10.1038/s44318-025-00406-3","DOIUrl":"10.1038/s44318-025-00406-3","url":null,"abstract":"Bacteria in polymicrobial habitats are constantly exposed to biotic threats from bacteriophages (or \"phages\"), antagonistic bacteria, and predatory eukaryotes. These antagonistic interactions play crucial roles in shaping the evolution and physiology of bacteria. To survive, bacteria have evolved mechanisms to protect themselves from such attacks, but the fitness costs of resisting one threat and rendering bacteria susceptible to others remain unappreciated. Here, we examined the fitness consequences of phage resistance in Salmonella enterica, revealing that phage-resistant variants exhibited significant fitness loss upon co-culture with competitor bacteria. These phage-resistant strains display varying degrees of lipopolysaccharide (LPS) deficiency and increased susceptibility to contact-dependent interbacterial antagonism, such as the type VI secretion system (T6SS). Utilizing mutational analyses and atomic force microscopy, we show that the long-modal length O-antigen of LPS serves as a protective barrier against T6SS-mediated intoxication. Notably, this competitive disadvantage can also be triggered independently by phages possessing LPS-targeting endoglycosidase in their tail spike proteins, which actively cleave the O-antigen upon infection. Our findings reveal two distinct mechanisms of phage-mediated LPS modifications that modulate interbacterial competition, shedding light on the dynamic microbial interplay within mixed populations.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2473-2500"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598323","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

SIRT5-mediated desuccinylation of PPA2 enhances HIF-1alpha-dependent adaptation to hypoxic stress and colorectal cancer metastasis. sirt5介导的PPA2去琥珀酰化增强了hif -1 α依赖的对缺氧应激和结直肠癌转移的适应。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-03-31 DOI: 10.1038/s44318-025-00416-1

Xiang Zhang, Yuqin Di, Youpeng Wang, Jiale Qin, Lvlan Ye, Xiangqiong Wen, Zunfu Ke, Ziyang Wang, Weiling He

{"title":"SIRT5-mediated desuccinylation of PPA2 enhances HIF-1alpha-dependent adaptation to hypoxic stress and colorectal cancer metastasis.","authors":"Xiang Zhang, Yuqin Di, Youpeng Wang, Jiale Qin, Lvlan Ye, Xiangqiong Wen, Zunfu Ke, Ziyang Wang, Weiling He","doi":"10.1038/s44318-025-00416-1","DOIUrl":"10.1038/s44318-025-00416-1","url":null,"abstract":"Metastasis is the primary cause of death in patients with colorectal cancer (CRC). Hypoxia is a hallmark of solid tumors that promotes cellular metabolic adaptation and dissemination. However, the mechanisms linking hypoxia-regulated metabolic adaptation to CRC metastasis remain unclear. Here, we found that inorganic pyrophosphatase 2 (PPA2) suppresses metastatic progression of CRC via its phosphatase function. PPA2 expression levels are reduced in CRC specimen and correlate with enhanced response to hypoxia by promoting hypoxia-inducible factor-1 (HIF-1) signaling to promote CRC cell glycolysis and dissemination. Mechanistically, PPA2 decreases HIF-1alpha stability through non-canonical ubiquitin-mediated proteasomal degradation via recruitment of E3 ligase NEDD4. Furthermore, PPA2 directly dephosphorylates NEDD4 at threonine 758 residue, resulting in its activation. Under hypoxic stress, NAD-dependent protein deacetylase sirtuin-5 promotes the dissociation of PPA2 and NEDD4 by inducing PPA2 desuccinylation at lysine 176, contributing to the improved stability of HIF-1alpha under hypoxic conditions. Our findings reveal a tumor-suppressive role of PPA2 in HIF-1alpha-dependent colorectal cancer, providing a potential therapeutic target and prognostic strategy.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2514-2540"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755566","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 selenocysteine-containing protein SELENOT maintains dopamine signaling in the midbrain to protect mice from hyperactivity disorder. 含硒半胱氨酸蛋白SELENOT维持中脑多巴胺信号，保护小鼠免受多动障碍。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1038/s44318-025-00430-3

Qing Guo, Zhao-Feng Li, Dong-Yan Hu, Pei-Jun Li, Kai-Nian Wu, Hui-Hui Fan, Jie Deng, Hong-Mei Wu, Xiong Zhang, Jian-Hong Zhu

{"title":"The selenocysteine-containing protein SELENOT maintains dopamine signaling in the midbrain to protect mice from hyperactivity disorder.","authors":"Qing Guo, Zhao-Feng Li, Dong-Yan Hu, Pei-Jun Li, Kai-Nian Wu, Hui-Hui Fan, Jie Deng, Hong-Mei Wu, Xiong Zhang, Jian-Hong Zhu","doi":"10.1038/s44318-025-00430-3","DOIUrl":"10.1038/s44318-025-00430-3","url":null,"abstract":"Dopaminergic neuron dysfunction has been implicated in multiple neurological and psychiatric disorders. SELENOT is a selenocysteine-containing protein of the ER membrane with antioxidant and neuroprotective activities, but its pathophysiological role in dopaminergic neurons remains unclear. In this study we show that male mice with SELENOT-deficient dopaminergic neurons exhibit attention deficit/hyperactivity disorder (ADHD)-like symptoms, including hyperlocomotion, recognition memory deficits, repetitive movements, and impulsivity. Dopamine metabolism, extrasynaptic dopamine levels, spontaneous excitatory postsynaptic currents in the striatum, and electroencephalography theta power are all enhanced in these animals, while dopaminergic neurons in the substantia nigra are slightly reduced but with normal firing and cellular stress levels. Our results also indicate that the expression of dopamine transporter (DAT) is significantly reduced in the absence of SELENOT. Both the development of ADHD-like phenotypes and DAT downregulation are also observed when SELENOT is absent from the whole brain, but not when its conditional knockout is restricted to astrocytes. Mechanistically, we show that SELENOT downregulates DAT expression via interaction with SERCA2 of the ER -but not with IP3R or RYR- to regulate the ER-cytosol Ca2+ flux and, subsequently, the activity of transcription factor NURR1 and the expression levels of DAT. Treatment with amphetamine or methylphenidate, which are commonly used to treat ADHD, reverses the hyperactivity observed in mice with SELENOT-deficient dopaminergic neurons. Our study demonstrates that SELENOT in mouse dopaminergic neurons maintains proper dopamine signaling in the midbrain against the development of ADHD-like behaviors.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2906-2927"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804600","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

Updated values for Table 1 of fastest rubisco carboxylation rates in Davidi et al 2020. david等人在2020年更新了表1中rubisco羧化最快速率的值。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1038/s44318-025-00419-y

Yi-Chin Candace Tsai, Zhijun Guo, Ron Milo, Oliver Mueller-Cajar

引用次数: 0

A double-agent microRNA regulates viral cross-kingdom infection in animals and plants. 一种双重作用的microRNA调节动物和植物的病毒跨界感染。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-03-05 DOI: 10.1038/s44318-025-00405-4

Wan Zhao, Hong Lu, Jiaming Zhu, Lan Luo, Feng Cui

引用次数: 0

Nuclear envelope-associated lipid droplets are enriched in cholesteryl esters and increase during inflammatory signaling. 核包膜相关的脂滴富含胆固醇酯，并在炎症信号传导过程中增加。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1038/s44318-025-00423-2

Ábel Szkalisity, Lauri Vanharanta, Hodaka Saito, Csaba Vörös, Shiqian Li, Antti Isomäki, Teemu Tomberg, Clare Strachan, Ilya Belevich, Eija Jokitalo, Elina Ikonen

{"title":"Nuclear envelope-associated lipid droplets are enriched in cholesteryl esters and increase during inflammatory signaling.","authors":"Ábel Szkalisity, Lauri Vanharanta, Hodaka Saito, Csaba Vörös, Shiqian Li, Antti Isomäki, Teemu Tomberg, Clare Strachan, Ilya Belevich, Eija Jokitalo, Elina Ikonen","doi":"10.1038/s44318-025-00423-2","DOIUrl":"10.1038/s44318-025-00423-2","url":null,"abstract":"Cholesteryl esters (CEs) and triacylglycerols (TAGs) are stored in lipid droplets (LDs), but their compartmentalisation is not well understood. Here, we established a hyperspectral stimulated Raman scattering microscopy system to identify and quantitatively assess CEs and TAGs in individual LDs of human cells. We found that nuclear envelope-associated lipid droplets (NE-LDs) were enriched in cholesteryl esters compared to lipid droplets in the cytoplasm. Correlative light-volume-electron microscopy revealed that NE-LDs projected towards the cytoplasm and associated with type II nuclear envelope (NE) invaginations. The nuclear envelope localization of sterol O-acyltransferase 1 (SOAT1) contributed to NE-LD generation, as trapping of SOAT1 to the NE further increased their number. Upon stimulation by the pro-inflammatory cytokine TNFα, the number of NE-LDs moderately increased. Moreover, TNFα-induced NF-κB nuclear translocation was fine-tuned by SOAT1: increased SOAT1 activity and NE-LDs associated with faster NF-κB translocation, whereas reduced SOAT1 activity and NE-LDs associated with slower NF-κB translocation. Our findings suggest that the NE is enriched in CEs and that cholesterol esterification can modulate nuclear translocation.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2774-2802"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804554","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

Interferon-induced PARP14-mediated ADP-ribosylation in p62 bodies requires the ubiquitin-proteasome system. 干扰素诱导的parp14介导的p62体adp核糖基化需要泛素-蛋白酶体系统。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1038/s44318-025-00421-4

Rameez Raja, Banhi Biswas, Rachy Abraham, Yiran Wang, Che-Yuan Chang, Ivo A Hendriks, Sara C Buch-Larsen, Hongrui Liu, Xingyi Yang, Chenyao Wang, Hien Vu, Anne Hamacher-Brady, Danfeng Cai, Anthony K L Leung

{"title":"Interferon-induced PARP14-mediated ADP-ribosylation in p62 bodies requires the ubiquitin-proteasome system.","authors":"Rameez Raja, Banhi Biswas, Rachy Abraham, Yiran Wang, Che-Yuan Chang, Ivo A Hendriks, Sara C Buch-Larsen, Hongrui Liu, Xingyi Yang, Chenyao Wang, Hien Vu, Anne Hamacher-Brady, Danfeng Cai, Anthony K L Leung","doi":"10.1038/s44318-025-00421-4","DOIUrl":"10.1038/s44318-025-00421-4","url":null,"abstract":"Biomolecular condensates are cellular compartments without enveloping membranes, enabling them to dynamically adjust their composition in response to environmental changes through post-translational modifications. Recent work has revealed that interferon-induced ADP-ribosylation (ADPr), which can be reversed by a SARS-CoV-2-encoded hydrolase, is enriched within a condensate. However, the identity of the condensate and the responsible host ADP-ribosyltransferase remain elusive. Here, we demonstrate that interferon induces ADPr through transcriptional activation of PARP14, requiring both the physical presence and catalytic activity of PARP14 for condensate formation. Interferon-induced ADPr colocalizes with PARP14 and its associated E3 ligase, DTX3L. These PARP14/ADPr condensates contain key components of p62 bodies-including the selective autophagy receptor p62, its binding partner NBR1 and the associated protein TAX1BP1, along with K48-linked and K63-linked polyubiquitin chains-but lack the autophagosome marker LC3B. Knockdown of p62 disrupts the formation of these ADPr condensates. Importantly, these structures are unaffected by autophagy inhibition, but depend on ubiquitination and proteasome activity. Taken together, these findings demonstrate that interferon triggers PARP14-mediated ADP-ribosylation in p62 bodies, which requires an active ubiquitin-proteasome system.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2741-2773"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804583","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

Meru co-ordinates spindle orientation with cell polarity and cell cycle progression. Meru协调纺锤体方向与细胞极性和细胞周期进程。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-04-01 DOI: 10.1038/s44318-025-00420-5

Melissa M McLellan, Birgit L Aerne, Jennifer J Banerjee Dhoul, Maxine V Holder, Tania Auchynnikava, Nicolas Tapon

{"title":"Meru co-ordinates spindle orientation with cell polarity and cell cycle progression.","authors":"Melissa M McLellan, Birgit L Aerne, Jennifer J Banerjee Dhoul, Maxine V Holder, Tania Auchynnikava, Nicolas Tapon","doi":"10.1038/s44318-025-00420-5","DOIUrl":"10.1038/s44318-025-00420-5","url":null,"abstract":"Correct mitotic spindle alignment is essential for tissue architecture and plays an important role in cell fate specification through asymmetric cell division. Spindle tethering factors such as Drosophila Mud (NuMA in mammals) are recruited to the cell cortex and capture astral microtubules, pulling the spindle in the correct orientation. However, how spindle tethering complexes read the cell polarity axis and how spindle attachment is coupled to mitotic progression remains poorly understood. We explore these questions in Drosophila sensory organ precursors (SOPs), which divide asymmetrically to give rise to epidermal mechanosensory bristles. We show that the scaffold protein Meru, which is enriched at the posterior cortex by the Frizzled/Dishevelled planar cell polarity complex, in turn recruits Mud, linking the spindle tethering and polarity machineries. Furthermore, Cyclin A/Cdk1 associates with Meru at the posterior cortex, promoting the formation of the Mud/Meru/Dsh complex via Meru and Dsh phosphorylation. Thus, Meru couples spindle orientation with cell polarity and provides a cell cycle-dependent cue for spindle tethering.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2949-2975"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765679","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

A bacterial network of T3SS effectors counteracts host pro-inflammatory responses and cell death to promote infection. 由 T3SS 效应器组成的细菌网络可抵消宿主的促炎反应和细胞死亡，从而促进感染。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-05-01 Epub Date: 2025-03-24 DOI: 10.1038/s44318-025-00412-5

Hui Wen Yeap, Ghin Ray Goh, Safwah Nasuha Rosli, Hai Shin Pung, Cristina Giogha, Vik Ven Eng, Jaclyn S Pearson, Elizabeth L Hartland, Kaiwen W Chen

{"title":"A bacterial network of T3SS effectors counteracts host pro-inflammatory responses and cell death to promote infection.","authors":"Hui Wen Yeap, Ghin Ray Goh, Safwah Nasuha Rosli, Hai Shin Pung, Cristina Giogha, Vik Ven Eng, Jaclyn S Pearson, Elizabeth L Hartland, Kaiwen W Chen","doi":"10.1038/s44318-025-00412-5","DOIUrl":"10.1038/s44318-025-00412-5","url":null,"abstract":"Innate immune signalling and cell death pathways are highly interconnected processes involving receptor-interacting protein kinases (RIPKs) as mediators of potent anti-microbial responses. However, these processes are often antagonised by bacterial type III secretion system (T3SS) effectors, and the cellular mechanisms by which the host retaliates are not completely understood. Here, we demonstrate that during Citrobacter rodentium infection, murine macrophages and colonic epithelial cells exhibit RIPK1 kinase-dependent caspase-8 activation to counteract NleE effector-mediated suppression of pro-inflammatory signalling. While C. rodentium injects into the host cells a second effector, NleB, to block caspase-8 signalling, macrophages respond by triggering RIPK3-mediated necroptosis, whereupon a third T3SS effector, EspL, acts to inactivate necroptosis. We further show that NleB and EspL collaborate to suppress caspase-8 and NLRP3 inflammasome activation in macrophages. Our findings suggest that C. rodentium has evolved to express a complex network of effectors as an adaptation to the importance of cell death for anti-bacterial defence in the host-pathogen arms race.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2424-2445"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701974","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