EMBO Journal最新文献_第4页

Making sense of oxygen sensing. 让氧气感应变得有意义。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-09-01 Epub Date: 2025-08-01 DOI: 10.1038/s44318-025-00513-1

Peter J Ratcliffe, Thomas P Keeley

引用次数: 0

Condensates of synaptic vesicles and synapsin-1 mediate actin sequestering and polymerization. 突触囊泡的凝聚物和突触蛋白-1介导肌动蛋白的分离和聚合。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-09-01 Epub Date: 2025-08-14 DOI: 10.1038/s44318-025-00516-y

Akshita Chhabra, Christian Hoffmann, Gerard Aguilar Pérez, Aleksandr A Korobeinikov, Jakob Rentsch, Nadja Hümpfer, Linda Kokwaro, Luka Gnidovec, Arsen Petrović, Jaqulin N Wallace, Johannes Vincent Tromm, Cristina Román-Vendrell, Emma C Johnson, Branislava Ranković, Eleonora Perego, Tommaso Volpi, Rubén Fernández-Busnadiego, Sarah Köster, Silvio O Rizzoli, Helge Ewers, Jennifer R Morgan, Dragomir Milovanović

{"title":"Condensates of synaptic vesicles and synapsin-1 mediate actin sequestering and polymerization.","authors":"Akshita Chhabra, Christian Hoffmann, Gerard Aguilar Pérez, Aleksandr A Korobeinikov, Jakob Rentsch, Nadja Hümpfer, Linda Kokwaro, Luka Gnidovec, Arsen Petrović, Jaqulin N Wallace, Johannes Vincent Tromm, Cristina Román-Vendrell, Emma C Johnson, Branislava Ranković, Eleonora Perego, Tommaso Volpi, Rubén Fernández-Busnadiego, Sarah Köster, Silvio O Rizzoli, Helge Ewers, Jennifer R Morgan, Dragomir Milovanović","doi":"10.1038/s44318-025-00516-y","DOIUrl":"10.1038/s44318-025-00516-y","url":null,"abstract":"Neuronal communication relies on precisely maintained synaptic vesicle (SV) clusters, which assemble via liquid-liquid phase separation. This process requires synapsins, the major synaptic phosphoproteins, which are known to bind actin. Reorganization of SVs, synapsins, and actin is a hallmark of synaptic activity, but the molecular details of the interactions between these components remain unclear. Here, we combine in vitro reconstitution with expansion microscopy, super-resolution imaging, and cryo-electron tomography to dissect the roles of SV-synapsin-1 condensates in the organization of the presynaptic actin cytoskeleton. Our results indicate that condensation of synapsin-1 initiates actin polymerization. This process enables SV-synapsin-actin assemblies to facilitate the mesoscale organization of SV clusters along axons, which is similar to the native presynaptic organization observed at both lamprey and mammalian synapses. Understanding the relationship between the actin network and synapsin-synaptic vesicle condensates can help elucidate how coordinated neurotransmission along the axon enables circuit function and behavior.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"5112-5148"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856946","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

NAC couples protein synthesis with nascent polypeptide myristoylation on the ribosome. NAC将蛋白质合成与核糖体上的新生多肽肉豆蔻酰化结合在一起。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-08-26 DOI: 10.1038/s44318-025-00548-4

Sara Zdancewicz, Emir Maldosevic, Kinga Malezyna, Ahmad Jomaa

{"title":"NAC couples protein synthesis with nascent polypeptide myristoylation on the ribosome.","authors":"Sara Zdancewicz, Emir Maldosevic, Kinga Malezyna, Ahmad Jomaa","doi":"10.1038/s44318-025-00548-4","DOIUrl":"https://doi.org/10.1038/s44318-025-00548-4","url":null,"abstract":"N-glycine myristoylation allows for reversible association of newly synthesized proteins with membranes to regulate essential functions such as cellular signaling and stress responses. This process can be catalyzed during protein synthesis by N-myristoyltransferases (NMTs), and its dysregulation has been implicated both in cancer and heart disease. Although the nascent polypeptide-associated complex (NAC) orchestrates the binding of several co-translational processing factors on ribosomes, its role in facilitating nascent protein myristoylation by NMT2 remains unclear. Here, we show that NAC mediates binding of NMT2 to translating ribosomes, which together form an extended channel that guides the nascent chain as it emerges from the polypeptide exit tunnel to the catalytic site of NMT2. Furthermore, the ternary ribosome:NMT2:NAC complex is stabilized by a ribosomal RNA clamp that, together with NAC, orients NMT2 on the ribosomal surface for co-translational myristoylation of nascent chains. Our work uncovers the molecular mechanism coupling protein synthesis to nascent protein myristoylation and underscores the role of NAC as a master regulator of protein biogenesis on the ribosome.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977179","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

Distinct filament morphology and membrane tethering features of the dual FtsZ paralogs in Odinarchaeota. 奥丁古菌双FtsZ相似物的独特纤维形态和膜系结特征。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-08-08 DOI: 10.1038/s44318-025-00529-7

Jayanti Kumari, Akhilesh Uthaman, Sucharita Bose, Ananya Kundu, Vaibhav Sharma, Soumyajit Dutta, Anubhav Dhar, Srijita Roy, Ramanujam Srinivasan, Samay Pande, Kutti R Vinothkumar, Pananghat Gayathri, Saravanan Palani

{"title":"Distinct filament morphology and membrane tethering features of the dual FtsZ paralogs in Odinarchaeota.","authors":"Jayanti Kumari, Akhilesh Uthaman, Sucharita Bose, Ananya Kundu, Vaibhav Sharma, Soumyajit Dutta, Anubhav Dhar, Srijita Roy, Ramanujam Srinivasan, Samay Pande, Kutti R Vinothkumar, Pananghat Gayathri, Saravanan Palani","doi":"10.1038/s44318-025-00529-7","DOIUrl":"10.1038/s44318-025-00529-7","url":null,"abstract":"The Asgard phylum has emerged as a model to study eukaryogenesis because of their close relatedness with the eukaryotes. In this study, we use FtsZ proteins from a member of the class Odinarchaeia as representatives to investigate the probable origin, evolution, and assembly of the FtsZ/tubulin protein superfamily in Asgard archaea. We performed a comparative analysis of the biochemical properties and cytoskeletal assembly of FtsZ1 and FtsZ2, the two FtsZ isoforms in the Odinarchaeota metagenome. Our electron microscopy analysis reveals that OdinFtsZ1 assembles into curved single protofilaments, while OdinFtsZ2 forms stacked spiral ring-like structures. Upon sequence analysis, we identified an N-terminal amphipathic helix in OdinFtsZ1, which mediates direct membrane tethering. In contrast, OdinFtsZ2 is recruited to the membrane by the anchor OdinSepF via OdinFtsZ2's C-terminal tail. Overall, we report the presence of two distant evolutionary paralogs of FtsZ in Odinarchaeota, with distinct filament assemblies and differing modes of membrane targeting. Our findings highlight the diversity of FtsZ proteins in the archaeal phylum Asgardarchaeota, providing valuable insights into the evolution and differentiation of tubulin-family proteins.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805218","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 million shades of green: understanding and harnessing plant metabolic diversity. 一百万种绿色：理解和利用植物代谢多样性。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-08-01 Epub Date: 2025-07-03 DOI: 10.1038/s44318-025-00496-z

Rocky D Payet, Adnane Aouidate, Rebecca Casson, Alan Houghton, Mai-Truc Pham, Anne Osbourn

引用次数: 0

Transcription factor IRF-5 regulates lipid metabolism and mitochondrial function in murine CD8⁺ T-cells during viral infection. 转录因子IRF-5在病毒感染期间调节小鼠CD8+ t细胞的脂质代谢和线粒体功能。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-08-01 Epub Date: 2025-06-10 DOI: 10.1038/s44318-025-00485-2

Linh Thuy Mai, Sharada Swaminathan, Trieu Hai Nguyen, Etienne Collette, Tania Charpentier, Liseth Carmona-Pérez, Hamza Loucif, Alain Lamarre, Krista M Heinonen, David Langlais, Jörg H Fritz, Simona Stäger

{"title":"Transcription factor IRF-5 regulates lipid metabolism and mitochondrial function in murine CD8+ T-cells during viral infection.","authors":"Linh Thuy Mai, Sharada Swaminathan, Trieu Hai Nguyen, Etienne Collette, Tania Charpentier, Liseth Carmona-Pérez, Hamza Loucif, Alain Lamarre, Krista M Heinonen, David Langlais, Jörg H Fritz, Simona Stäger","doi":"10.1038/s44318-025-00485-2","DOIUrl":"10.1038/s44318-025-00485-2","url":null,"abstract":"Exhaustion of CD8+ T-cells leads to their reduced immune functionality and is controlled by numerous transcription factors. Here we show that the transcription factor IRF-5 helps to limit functional exhaustion of murine CD8+ T-cells during the chronic stage of LCMV (CL13) viral infection. Our results suggest that T-cell inhibitory receptors and transcription factor TOX, which are implicated in dampening T-cell activation and promoting exhaustion, are upregulated in infected IRF-5-deficient CD8+ T-cells. In addition, these cells display a reduced capacity to produce cytokines and lower survival rates than wild-type cells. Our findings indicate that these effects are mediated by defective lipid metabolism, increased lipid peroxidation, enhanced mitochondrial ROS production, and reduced levels of oxidative phosphorylation in the absence of IRF-5. These results identify IRF-5 as an important regulator of lipid metabolism and mitochondrial function that protects CD8+ T-cells from functional exhaustion during the chronic stage of viral infection.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"4280-4300"},"PeriodicalIF":8.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267804","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 proteostatic landscape of healthy human oocytes. 健康人类卵母细胞的蛋白酶抑制景观。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-08-01 Epub Date: 2025-07-16 DOI: 10.1038/s44318-025-00493-2

Gabriele Zaffagnini, Miquel Solé, Juan Manuel Duran, Nikolaos P Polyzos, Elvan Böke

{"title":"The proteostatic landscape of healthy human oocytes.","authors":"Gabriele Zaffagnini, Miquel Solé, Juan Manuel Duran, Nikolaos P Polyzos, Elvan Böke","doi":"10.1038/s44318-025-00493-2","DOIUrl":"10.1038/s44318-025-00493-2","url":null,"abstract":"Oocytes, female germ cells that develop into eggs, are among the longest-lived cells in the animal body. Recent studies on mouse oocytes highlight unique adaptations in protein homeostasis (proteostasis) within these cells. However, the mechanisms of proteostasis in human oocytes remain virtually unstudied. We present the first large-scale study of proteostatic activity in human oocytes using over 100 freshly donated oocytes from 21 healthy women aged 19-34 years. We analysed the activity and distribution of lysosomes, proteasomes, and mitochondria in both immature and mature oocytes. Notably, human oocytes exhibit nearly twofold lower proteolytic activity than surrounding somatic cells, with further decreases as oocytes mature. Oocyte maturation is also coupled with lysosomal exocytosis and a decrease in mitochondrial membrane potential. We propose that reduced organelle activity preserves key cellular components critical for early embryonic development during the prolonged maturation of human oocytes. Our findings highlight the distinctive biology of human oocytes and the need to investigate human-specific reproductive biology to address challenges in female fertility.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"4611-4630"},"PeriodicalIF":8.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651116","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

Master transcription-factor binding sites constitute the core of early replication control elements. 主转录因子结合位点构成早期复制控制元件的核心。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-08-01 Epub Date: 2025-07-17 DOI: 10.1038/s44318-025-00501-5

Jesse L Turner, Laura Hinojosa-Gonzalez, Takayo Sasaki, Satoshi Uchino, Athanasios Vouzas, Mariella S Soto, Abhijit Chakraborty, Karen E Alexander, Cheryl A Fitch, Amber N Brown, Ferhat Ay, David M Gilbert

{"title":"Master transcription-factor binding sites constitute the core of early replication control elements.","authors":"Jesse L Turner, Laura Hinojosa-Gonzalez, Takayo Sasaki, Satoshi Uchino, Athanasios Vouzas, Mariella S Soto, Abhijit Chakraborty, Karen E Alexander, Cheryl A Fitch, Amber N Brown, Ferhat Ay, David M Gilbert","doi":"10.1038/s44318-025-00501-5","DOIUrl":"10.1038/s44318-025-00501-5","url":null,"abstract":"Eukaryotic genomes replicate in a defined temporal order called the replication timing (RT) program. RT is developmentally regulated with the potential to drive cell fate transitions, but mechanisms controlling RT remain elusive. We previously identified \"Early Replication Control Elements\" (ERCEs), cis-acting elements necessary for early RT, domain-wide transcription, 3D chromatin architecture and compartmentalization in mouse embryonic stem cells (mESCs), but deletions identifying ERCEs were large and encompassed many putative regulatory elements. Here, we show that ERCEs are compound elements, whose RT activity can largely be accounted for by multiple binding sites for diverse master transcription factors (subERCEs). While deletion of subERCEs had large effects on both transcription and replication timing, deleting transcription start sites eliminated nearly all transcription with only moderate effects on replication timing. Our results suggest a model in which subERCEs are a class of transcriptional enhancers that can also organize chromatin domains structurally to support early replication timing, potentially providing a feed-forward loop to drive robust epigenomic change during cell fate transitions.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"4499-4524"},"PeriodicalIF":8.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660958","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

TERRA R-loops trigger a switch in telomere maintenance towards break-induced replication and PRIMPOL-dependent repair. TERRA r -环触发端粒维护向断裂诱导复制和primpol依赖性修复的开关。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-08-01 Epub Date: 2025-07-07 DOI: 10.1038/s44318-025-00502-4

Suna In, Patricia Renck Nunes, Rita Valador Fernandes, Joachim Lingner

{"title":"TERRA R-loops trigger a switch in telomere maintenance towards break-induced replication and PRIMPOL-dependent repair.","authors":"Suna In, Patricia Renck Nunes, Rita Valador Fernandes, Joachim Lingner","doi":"10.1038/s44318-025-00502-4","DOIUrl":"10.1038/s44318-025-00502-4","url":null,"abstract":"TERRA long noncoding RNAs associate with telomeres post transcription through base-pairing with telomeric DNA forming R-loop structures. TERRA regulates telomere maintenance but its exact modes of action remain unknown. Here, we induce TERRA transcription and R-loop formation in telomerase-expressing cells and determine that TERRA R-loop formation requires non-redundant functions of the RAD51 DNA recombinase and its enhancer RAD51AP1. TERRA R-loops interfere with semiconservative DNA replication, promoting telomere maintenance by a homology-directed repair (HDR) mechanism known as break-induced replication (BIR), which ensures telomere maintenance in ALT cancer cells. In addition, TERRA induces PRIMPOL-dependent repair, which can initiate DNA synthesis de novo downstream of replication obstacles. PRIMPOL acts in parallel to BIR for telomere maintenance of TERRA-overexpressing cells, promoting their survival. Similarly, we find that PRIMPOL depletion is synthetic-lethal with BIR deficiency in U2OS ALT cancer cells. Therefore, TERRA R-loops by themselves are sufficient to induce ALT-typical telomere repair mechanisms, in the absence of other ALT-typical telomeric chromatin changes.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"4525-4551"},"PeriodicalIF":8.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585558","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

Optochemical profiling of NMDAR molecular diversity at synaptic and extrasynaptic sites. 突触和突触外NMDAR分子多样性的光化学分析。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2025-08-01 Epub Date: 2025-07-08 DOI: 10.1038/s44318-025-00498-x

Antoine Sicard, Meilin Tian, Zakaria Mostefai, Sophie Shi, Cécile Cardoso, Joseph Zamith, Isabelle McCort-Tranchepain, Cécile Charrier, Pierre Paoletti, Laetitia Mony

{"title":"Optochemical profiling of NMDAR molecular diversity at synaptic and extrasynaptic sites.","authors":"Antoine Sicard, Meilin Tian, Zakaria Mostefai, Sophie Shi, Cécile Cardoso, Joseph Zamith, Isabelle McCort-Tranchepain, Cécile Charrier, Pierre Paoletti, Laetitia Mony","doi":"10.1038/s44318-025-00498-x","DOIUrl":"10.1038/s44318-025-00498-x","url":null,"abstract":"Neurotransmitter receptors are critical for neuronal communication. They often form large multimeric complexes that differ in their subunit composition, distribution, and signaling properties. N-methyl-D-aspartate receptors (NMDARs), a class of glutamate-gated ion channels with essential roles in brain development and plasticity, co-exist as multiple subtypes, with GluN2A diheteromers, GluN2B diheteromers, and GluN2A/GluN2B triheteromers prevailing in the adult forebrain. Studying individual subtypes in native tissues with subunit stoichiometry resolution remains challenging, and the relative abundance and subcellular distribution of these subtypes remain controversial. Here we develop and use the photochemical tool Opto2B for specific and reversible modulation of GluN2B diheteromers, while leaving other receptor subtypes (in particular GluN2A/GluN2B triheteromers) unaffected. Using Opto2B, we characterize the differential contribution of GluN2B diheteromers to synaptic and extrasynaptic NMDAR pools during mouse development. Our results suggest that GluN2A receptors predominate in both pools in adult hippocampal CA1 pyramidal cells, with no preferential contribution of GluN2B diheteromers to extrasynaptic currents, challenging the common view that GluN2A and GluN2B NMDARs segregate in synaptic and extrasynaptic compartments, respectively. Our study addresses long-standing questions on extrasynaptic NMDARs and paves the way for interrogating NMDAR signaling diversity with unprecedented molecular and spatio-temporal resolution.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"4577-4610"},"PeriodicalIF":8.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592851","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