The EMBO Journal最新文献_第4页

Essential nucleus-apical pole linkage maintains division fidelity during Plasmodium progeny formation. 在疟原虫子代形成过程中，必要的核-顶极连锁维持了分裂的保真度。

The EMBO Journal Pub Date : 2026-07-03 DOI: 10.1038/s44318-026-00836-7

Buyuan He,Ilzat Ali,Lilian P Dorner,Monami Roy Chowdhury,Yvonne Sokolowski-Adams,Evgeniya Abadzhieva,Arne Reich,Marilena Wittmaack,Julia M Sattler,Friedrich Frischknecht,Jeffrey D Dvorin

{"title":"Essential nucleus-apical pole linkage maintains division fidelity during Plasmodium progeny formation.","authors":"Buyuan He,Ilzat Ali,Lilian P Dorner,Monami Roy Chowdhury,Yvonne Sokolowski-Adams,Evgeniya Abadzhieva,Arne Reich,Marilena Wittmaack,Julia M Sattler,Friedrich Frischknecht,Jeffrey D Dvorin","doi":"10.1038/s44318-026-00836-7","DOIUrl":"https://doi.org/10.1038/s44318-026-00836-7","url":null,"abstract":"Plasmodium parasites, the causative agents of malaria, undergo complex replication within vertebrate and insect hosts, presenting unique opportunities for therapeutic intervention. A key challenge during these replication events, i.e., schizogony in vertebrate red blood cells and sporogony in oocysts within mosquitos, is ensuring the faithful partitioning of nuclei and organelles into the numerous daughter cells that form at once from a single parental cell. While nuclear microtubule-organizing centers, or centriolar plaques (CPs), have been hypothesized to play a central role in this process, the molecular mediators linking CPs and organelles remain incompletely defined. Here, we characterize the roles of two striated fiber assemblin (SFA) homologs, SFA1 and SFA2, in replication of Plasmodium falciparum and Plasmodium berghei across two hosts. We show that these SFAs form a physical bridge between the CP and the nascent apical poles of daughter cells, facilitating high-fidelity progeny formation during schizogony and sporogony. Loss of SFA function disrupts merozoite and sporozoite formation, with profound consequences for transmission. These findings identify striated fiber assemblins as essential organizers of parasite morphogenesis and potential targets for anti-malarial therapies.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From cell atlases to mechanisms: bridging scRNA-seq discovery with in vivo genetics. 从细胞图谱到机制：连接scRNA-seq发现与体内遗传学。

The EMBO Journal Pub Date : 2026-07-03 DOI: 10.1038/s44318-026-00846-5

Bin Zhou

引用次数: 0

Assembly of the catalytic module and the rotor of human ATP synthase. 人ATP合酶催化模块与转子的组装。

The EMBO Journal Pub Date : 2026-06-26 DOI: 10.1038/s44318-026-00842-9

Jiuya He,Joe Carroll,Shujing Ding,Jiao Li,Ian M Fearnley,John E Walker

{"title":"Assembly of the catalytic module and the rotor of human ATP synthase.","authors":"Jiuya He,Joe Carroll,Shujing Ding,Jiao Li,Ian M Fearnley,John E Walker","doi":"10.1038/s44318-026-00842-9","DOIUrl":"https://doi.org/10.1038/s44318-026-00842-9","url":null,"abstract":"Human ATP synthase is a molecular rotary machine bound in inner mitochondrial membranes, built from twenty-eight subunits of seventeen kinds, two encoded in mitochondrial DNA, the remainder in nuclear genes. The machine consists of a rotor and an interacting stator. Turning of the rotor driven by a transmembrane proton motive force effects a cycle of structural changes in the catalytic part of the stator, producing three ATP molecules per rotation. Here, to establish how the stator and rotor are assembled, we deleted subunits and known assembly factors from human cells, purified and accumulated assembly intermediate complexes, and characterized them by gel analysis and mass spectrometry, allowing us to propose pathways of assembly of the rotor and the catalytic F1-module of the stator. These observations provide opportunities for further development by structural analysis of the accumulated intermediates. The compositions of the various assembly intermediates support the view that ATP synthase arose via independent evolution of its three constituent structural components, the catalytic F1-module, the peripheral stalk module, and the membrane-associated Fo-module.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular assembly and functional resilience of the mammalian RNA exosome. 哺乳动物RNA外泌体的细胞组装和功能恢复。

The EMBO Journal Pub Date : 2026-06-25 DOI: 10.1038/s44318-026-00824-x

Tsimafei Navalayeu,Nikolaus Beer,Monika Bebjaková,Robert W Kalis,Ulrich Hohmann,Karel Stejskal,Gabriela Krššáková,Nina Fasching,Veronika A Herzog,Niko Popitsch,Elisabeth Roitinger,Clemens Plaschka,Johannes Zuber,Stefan L Ameres

{"title":"Cellular assembly and functional resilience of the mammalian RNA exosome.","authors":"Tsimafei Navalayeu,Nikolaus Beer,Monika Bebjaková,Robert W Kalis,Ulrich Hohmann,Karel Stejskal,Gabriela Krššáková,Nina Fasching,Veronika A Herzog,Niko Popitsch,Elisabeth Roitinger,Clemens Plaschka,Johannes Zuber,Stefan L Ameres","doi":"10.1038/s44318-026-00824-x","DOIUrl":"https://doi.org/10.1038/s44318-026-00824-x","url":null,"abstract":"Most eukaryotic proteins assemble into multisubunit complexes that coordinate essential cellular functions, yet the principles governing their assembly and proteostatic control remain largely undefined. Here, we systematically dissect the cellular assembly and functional organization of the RNA exosome, an essential ribonucleolytic complex, using an inducible dual-guide CRISPR/Cas9 system in mouse embryonic stem cells. We reveal a sequential assembly pathway where Exosc2, Exosc4, and Exosc7 initiate complex formation, facilitating the incorporation of barrel and cap subunits in a defined hierarchy. Unlike other structural subunits, the terminally incorporated cap subunit Exosc1 is dispensable for cell viability, revealing a modular, functionally resilient architecture. We demonstrate that orphan subunits are selectively degraded via the ubiquitin-proteasome system, enforcing stringent quality control over RNA exosome biogenesis. These findings define an assembly logic of of the mammalian exosome and uncover previously unrecognized plasticity in the composition and function of this essential ribonucleolytic complex.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148322583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

OMA1 protects from liver injury and tumorigenesis during aging by controlling hepatic immunogenicity. OMA1通过控制肝脏免疫原性保护衰老过程中的肝损伤和肿瘤发生。

The EMBO Journal Pub Date : 2026-06-23 DOI: 10.1038/s44318-026-00839-4

Yolanda Martí-Mateos,María Del Mar Muñoz-Hernández,Manuel M Gómez de Las Heras,José Ignacio Escrig-Larena,José Luis Cabrera-Alarcón,Rebeca Acín-Pérez,Enrique Calvo,Sara Natalia Jaroszewicz,Lucía de Prado-Rivas,Eva Raquel Martínez-Jiménez,Macarena De Andrés-Laguillo,Esther García-Domínguez,María Carmen Gómez-Cabrera,José Viña,Rui Benedito,Alejo Efeyan,Jesús Vázquez,María Mittelbrunn,María Concepción Jiménez-Gómez,José Antonio Enríquez

{"title":"OMA1 protects from liver injury and tumorigenesis during aging by controlling hepatic immunogenicity.","authors":"Yolanda Martí-Mateos,María Del Mar Muñoz-Hernández,Manuel M Gómez de Las Heras,José Ignacio Escrig-Larena,José Luis Cabrera-Alarcón,Rebeca Acín-Pérez,Enrique Calvo,Sara Natalia Jaroszewicz,Lucía de Prado-Rivas,Eva Raquel Martínez-Jiménez,Macarena De Andrés-Laguillo,Esther García-Domínguez,María Carmen Gómez-Cabrera,José Viña,Rui Benedito,Alejo Efeyan,Jesús Vázquez,María Mittelbrunn,María Concepción Jiménez-Gómez,José Antonio Enríquez","doi":"10.1038/s44318-026-00839-4","DOIUrl":"https://doi.org/10.1038/s44318-026-00839-4","url":null,"abstract":"Hepatic inflammation and immunosurveillance play major roles in the progression of liver cancer. A common trigger for hepatic inflammation is oxidative stress, which stems from mitochondrial dysfunction. Here, we demonstrate that deletion of the mitochondrial stress integrator OMA1 increases hepatic primary tumor incidence and impairs survival in mice. Persistent activation of the KEAP1-Nrf2 oxidative stress pathway in the absence of OMA1 promotes early liver injury, which progresses into chronic hepatic inflammation and fibrosis during aging. Exhausted CD8+ and CD4+ T cells gradually accumulate in Oma1KO livers, facilitating hepatic tumor progression. Adoptive transfer and bone marrow-transplant experiments indicate that hepatic immunogenicity increases in the absence of parenchymal OMA1. Furthermore, hepatocyte-specific Oma1 deletion is sufficient to trigger NRF2 signaling, hepatocyte death, and immune exhaustion, suggesting that immunosurveillance during liver aging relies on the hepatic expression of OMA1. Given the therapeutic interest of OMA1 in several pathologies, these data are crucial to guide the generation of safe OMA1-targeted therapies.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

mRAVE governs lysosomal catabolism through basal and mTORC1-regulated V-ATPase assembly. mRAVE通过基础和mtorc1调节的v - atp酶组装来控制溶酶体分解代谢。

The EMBO Journal Pub Date : 2026-06-22 DOI: 10.1038/s44318-026-00838-5

Nora S Siefert,Andrea Zanotti,Anastasija Paneva,Martin Schneider,Dominic Helm,Wilhelm Palm

{"title":"mRAVE governs lysosomal catabolism through basal and mTORC1-regulated V-ATPase assembly.","authors":"Nora S Siefert,Andrea Zanotti,Anastasija Paneva,Martin Schneider,Dominic Helm,Wilhelm Palm","doi":"10.1038/s44318-026-00838-5","DOIUrl":"https://doi.org/10.1038/s44318-026-00838-5","url":null,"abstract":"Acidification of lysosomes, endosomes and the Golgi underpins organelle-specific functions within the endomembrane system. This process is driven by vacuolar-type H + -ATPases (V-ATPases), proton pumps that reversibly assemble from peripheral V1 and membrane-integral Vo domains to regulate organelle pH. In yeast, V1-Vo assembly at the vacuole is mediated by the RAVE complex, but V-ATPase assembly in mammalian cells remains less well understood. Here, we systematically characterize physiological roles of the mammalian RAVE complex, composed of the subunits Dmxl1 or Dmxl2, Wdr7 and Rogdi. Under basal conditions, mRAVE broadly promotes V-ATPase assembly and luminal acidification of endomembrane organelles. Upon mTORC1 inactivation, mRAVE is recruited to lysosomes and required for the resulting increase in V-ATPase assembly and catabolic activity. Loss of mRAVE disrupts organelle acidification, leading to suppression of lysosomal catabolism, accumulation of dysfunctional lysosomes and lysosomal exocytosis. Restoring lysosomal pH rescues basal function in mRAVE-deficient cells but not the mTORC1-regulated increase in catabolic activity. Thus, mRAVE is an essential V-ATPase assembly factor that couples acidification to organelle function and nutrient signaling.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RYBP regulates selective genomic binding of TrxG and PcG components in embryonic stem cell fate control. RYBP调控TrxG和PcG组分在胚胎干细胞命运控制中的选择性基因组结合。

The EMBO Journal Pub Date : 2026-04-28 DOI: 10.1038/s44318-026-00788-y

Chao Wei,Jun Sun,Zhuoyan Liu,Mulan Wang,Jin Tan,Xiaona Huang,Ranran Dai,Kang Su,Shiwen Yang,Tara S R Chen,Qi Tian,Xiuxiao Tang,Xiaolin Tian,Dong-Feng Huang,Jin Bai,Xue Xiao,Xiaoting Shen,Juan Xia,Junjun Ding,Lili Fan

{"title":"RYBP regulates selective genomic binding of TrxG and PcG components in embryonic stem cell fate control.","authors":"Chao Wei,Jun Sun,Zhuoyan Liu,Mulan Wang,Jin Tan,Xiaona Huang,Ranran Dai,Kang Su,Shiwen Yang,Tara S R Chen,Qi Tian,Xiuxiao Tang,Xiaolin Tian,Dong-Feng Huang,Jin Bai,Xue Xiao,Xiaoting Shen,Juan Xia,Junjun Ding,Lili Fan","doi":"10.1038/s44318-026-00788-y","DOIUrl":"https://doi.org/10.1038/s44318-026-00788-y","url":null,"abstract":"Selective gene expression is pivotal in orchestrating human development. Specifically, trithorax group (TrxG) and polycomb group (PcG) components play crucial roles in transcriptional activation and repression of state-specific stem cell expression programs, yet the mechanisms underlying their selective genomic binding remain poorly understood. In this study, we report that the polycomb repressive complex 1 (PRC1) subunit RYBP co-localizes with TrxG component WDR5 and selectively enriches PcG component RING1B in condensates in murine embryonic stem cells (ESCs). RYBP deficiency impairs the genomic binding of WDR5 and RING1B. Further, STAT3 excludes RING1B binding at RYBP-associated transcriptionally active loci. Additionally, RYBP depletion attenuates WDR5-dependent activation of DNA repair gene expression and facilitates the transition of ESCs to 2-cell-like cells. Finally, RYBP depletion disrupts RING1B deposition at lineage-specific genes, promoting ESC differentiation towards mesendoderm fate. These findings uncover RYBP as a regulator of selective genomic binding of TrxG and PcG components, providing insights into their roles in cell fate determination during development.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quiescent neural stem cells transiently become neuron-like to coordinate long-range reactivation. 静止的神经干细胞瞬间变成神经元样以协调远程再激活。

The EMBO Journal Pub Date : 2026-04-24 DOI: 10.1038/s44318-026-00775-3

Laura-Yvonne Gherghina,Jocelyn L Y Tang,Leo Otsuki,Leia Judge,Andrea H Brand

引用次数: 0

Tissue-selective COPII modulator SEC16B aggravates cardiovascular disease by promoting lipid export. 组织选择性COPII调节剂SEC16B通过促进脂质输出加重心血管疾病。

The EMBO Journal Pub Date : 2026-04-24 DOI: 10.1038/s44318-026-00754-8

Xiao Wang,Yating Hu,Lu Liu,Runze Huang,Yawei Wang,Bing Liu,Yifei Zhao,Yuangang Zhu,Jia Lv,Liang Liu,Huimin Wang,Lingzhi Wu,Xinxuan Xu,Yaxin Li,Guanlin Wang,Xiao-Wei Chen

{"title":"Tissue-selective COPII modulator SEC16B aggravates cardiovascular disease by promoting lipid export.","authors":"Xiao Wang,Yating Hu,Lu Liu,Runze Huang,Yawei Wang,Bing Liu,Yifei Zhao,Yuangang Zhu,Jia Lv,Liang Liu,Huimin Wang,Lingzhi Wu,Xinxuan Xu,Yaxin Li,Guanlin Wang,Xiao-Wei Chen","doi":"10.1038/s44318-026-00754-8","DOIUrl":"https://doi.org/10.1038/s44318-026-00754-8","url":null,"abstract":"The biogenesis and transport of lipoproteins are essential for systemic homeostasis and cardiometabolic health, yet how the secretory pathway acquires specialization to support high-capacity lipoprotein export remains unclear. Here, we report SEC16B as a tissue-selective modulator of the COPII machinery, critical for the efficient secretion of APOB-containing lipoproteins. Integrative bioinformatic analyses identify that SEC16B co-emerges with core genes involved in lipoprotein biogenesis. Functional studies, coupled with AI-driven prediction, reveal that SEC16B acts as a molecular brake to fine-tune COPII condensation for lipoprotein export. Mining of UK biobank data links SEC16B to metabolic traits in humans and suggests HNF4A-dependent regulation of SEC16B expression. Hepatic deletion of SEC16B in mice markedly reduces circulating APOB, triglycerides and cholesterol, while conferring robust protection against atherosclerosis and cardiac dysfunction and maintaining liver health. Collectively, these findings position SEC16B as a specialized modulator of lipoprotein export via the general secretory (SEC) pathway in the liver, suggesting potential therapeutic avenues for combating cardiometabolic diseases.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure-guided optimization of SLC1A1/EAAT3-selective inhibitors targeting renal cancer metabolism. 针对肾癌代谢的SLC1A1/ eaat3选择性抑制剂的结构导向优化

The EMBO Journal Pub Date : 2026-04-22 DOI: 10.1038/s44318-026-00776-2

Pooneh Koochaki,Biao Qiu,Jesse A Coker,Alexander Earsley,Nancy S Wang,Todd Romigh,Christopher M Goins,Carleigh Salem,Dehui Mi,Emily Days,Joshua A Bauer,Shaun R Stauffer,Olga Boudker,Abhishek A Chakraborty

{"title":"Structure-guided optimization of SLC1A1/EAAT3-selective inhibitors targeting renal cancer metabolism.","authors":"Pooneh Koochaki,Biao Qiu,Jesse A Coker,Alexander Earsley,Nancy S Wang,Todd Romigh,Christopher M Goins,Carleigh Salem,Dehui Mi,Emily Days,Joshua A Bauer,Shaun R Stauffer,Olga Boudker,Abhishek A Chakraborty","doi":"10.1038/s44318-026-00776-2","DOIUrl":"https://doi.org/10.1038/s44318-026-00776-2","url":null,"abstract":"Renal cell carcinomas (RCCs) depend on the trimeric sodium-coupled aspartate and glutamate transporter, SLC1A1/EAAT3; however, pharmacologically targeting SLC1A1 is challenging. Here we determined a cryo-EM structure of human SLC1A1 bound to compound 3e, a recently described SLC1A1-selective bicyclic imidazo[1,2 α]pyridine-3-amine (BIA) inhibitor with an unclear mechanism of action. 3e binds a membrane-embedded allosteric pocket accessible only in the apo state, when SLC1A1 is unbound to substrate and sodium, and likely prevents sodium and substrate binding. Moreover, by forming a wedge between the trimerization domain and the substrate-binding transport domain, alongside a cholesterol moiety from the lipid bilayer, 3e blocks SLC1A1's elevator-like movements that support the transport cycle. Mutations in this binding pocket abolish the 3e interaction and counteract 3e's cytotoxicity in RCC cells, confirming on-target activity and explaining SLC1A1 selectivity. The subsequent design of two new SLC1A1-selective BIA derivatives, PBJ1 and PBJ2, was directed by the SLC1A1-3e structures; both inhibited SLC1A1-dependent aspartate, glutamate, and cysteine metabolism and showed enhanced cytotoxicity.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0