EMBO Reports最新文献_第5页

Peptide-based recycling of critical raw materials from electronic waste : The transition towards a circular economy requires novel and environmentally-friendly solutions to increase the recycling rate from discarded electronic devices. 基于多肽的电子废物关键原材料回收：向循环经济的过渡需要新颖和环保的解决方案，以提高废弃电子设备的回收率。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-23 DOI: 10.1038/s44319-025-00449-x

Franziska L Lederer, Peter Boelens

引用次数: 0

Mpf1 affects the dual distribution of tail-anchored proteins between mitochondria and peroxisomes. Mpf1影响尾锚蛋白在线粒体和过氧化物酶体之间的双重分布。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-02 DOI: 10.1038/s44319-025-00440-6

Nitya Aravindan, Daniela G Vitali, Julia Breuer, Jessica Oberst, Einat Zalckvar, Maya Schuldiner, Doron Rapaport

{"title":"Mpf1 affects the dual distribution of tail-anchored proteins between mitochondria and peroxisomes.","authors":"Nitya Aravindan, Daniela G Vitali, Julia Breuer, Jessica Oberst, Einat Zalckvar, Maya Schuldiner, Doron Rapaport","doi":"10.1038/s44319-025-00440-6","DOIUrl":"10.1038/s44319-025-00440-6","url":null,"abstract":"Most cellular proteins require targeting to a distinct cellular compartment to function properly. A subset of proteins is distributed to two or more destinations in the cell and little is known about the mechanisms controlling the process of dual/multiple targeting. Here, we provide insight into the mechanism of dual targeting of proteins between mitochondria and peroxisomes. We perform a high throughput microscopy screen in which we visualize the location of the model tail-anchored proteins Fis1 and Gem1 in the background of mutants in virtually all yeast genes. This screen identifies three proteins, whose absence results in a higher portion of the tail-anchored proteins in peroxisomes: the two paralogues Tom70, Tom71, and the uncharacterized gene YNL144C that we rename mitochondria and peroxisomes factor 1 (Mpf1). We characterize Mpf1 to be an unstable protein that associates with the cytosolic face of the mitochondrial outer membrane. Furthermore, our study uncovers a unique contribution of Tom71 to the regulation of dual targeting. Collectively, our study reveals, for the first time, factors that influence the dual targeting of proteins between mitochondria and peroxisomes.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2622-2653"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771688","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

TLR4 endocytosis and endosomal TLR4 signaling are distinct and independent outcomes of TLR4 activation. TLR4内吞作用和内体TLR4信号是TLR4激活的不同且独立的结果。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-09 DOI: 10.1038/s44319-025-00444-2

Thomas E Schultz, Carmen D Mathmann, Leslie C Domínguez Cadena, Timothy W Muusse, Hyoyoung Kim, James W Wells, Glen C Ulett, Jessica A Hamerman, Andrew J Brooks, Bostjan Kobe, Matthew J Sweet, Katryn J Stacey, Antje Blumenthal

{"title":"TLR4 endocytosis and endosomal TLR4 signaling are distinct and independent outcomes of TLR4 activation.","authors":"Thomas E Schultz, Carmen D Mathmann, Leslie C Domínguez Cadena, Timothy W Muusse, Hyoyoung Kim, James W Wells, Glen C Ulett, Jessica A Hamerman, Andrew J Brooks, Bostjan Kobe, Matthew J Sweet, Katryn J Stacey, Antje Blumenthal","doi":"10.1038/s44319-025-00444-2","DOIUrl":"10.1038/s44319-025-00444-2","url":null,"abstract":"Toll-like receptor 4 (TLR4) signaling at the plasma membrane and in endosomes results in distinct contributions to inflammation and host defence. Current understanding indicates that endocytosis of cell surface-activated TLR4 is required to enable subsequent signaling from endosomes. Contrary to this prevailing model, our data show that endosomal TLR4 signaling is not reliant on cell surface-expressed TLR4 or ligand-induced TLR4 endocytosis. Moreover, previously recognized requirements for the accessory molecule CD14 in TLR4 endocytosis and endosomal signaling are likely attributable to CD14 binding as well as trafficking and transferring lipopolysaccharide (LPS) to TLR4 at different subcellular localizations. TLR4 endocytosis requires the TLR4 intracellular signaling domain, contributions by phospholipase C gamma 2, spleen tyrosine kinase, E1/E2 ubiquitination enzymes, but not canonical TLR signaling adaptors and cascades. Thus, our study identifies independently operating TLR4 signaling modes that control TLR4 endocytosis, pro-inflammatory cell surface-derived, as well as endosomal TLR4 signaling. This revised understanding of how TLR4 functions within cells might be harnessed to selectively amplify or restrict TLR4 activation for the development of adjuvants, vaccines and therapeutics.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2740-2766"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986080","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

Author Correction: Genotoxic stress triggers Scd6-dependent regulation of translation to modulate the DNA damage response. 作者更正：基因毒性应激触发scd6依赖的翻译调节，以调节DNA损伤反应。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 DOI: 10.1038/s44319-025-00481-x

Gayatri Mohanan, Raju Roy, Hélène Malka-Mahieu, Swati Lamba, Lucilla Fabbri, Sidhant Kalia, Anusmita Biswas, Sylvain Martineau, Céline M Labbé, Stéphan Vagner, Purusharth I Rajyaguru

引用次数: 0

Developmental epigenetic programming by Tet1/3 determines peripheral CD8 T cell fate. Tet1/3的发育表观遗传编程决定外周CD8 T细胞的命运。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-02 DOI: 10.1038/s44319-025-00439-z

Kara M Misel-Wuchter, Andrew L Thurman, Jordan T Johnson, Athmane Teghanemt, Neelam Gautam, Alejandro A Pezzulo, Jennifer R Bermick, Noah S Butler, Priya D Issuree

{"title":"Developmental epigenetic programming by Tet1/3 determines peripheral CD8 T cell fate.","authors":"Kara M Misel-Wuchter, Andrew L Thurman, Jordan T Johnson, Athmane Teghanemt, Neelam Gautam, Alejandro A Pezzulo, Jennifer R Bermick, Noah S Butler, Priya D Issuree","doi":"10.1038/s44319-025-00439-z","DOIUrl":"10.1038/s44319-025-00439-z","url":null,"abstract":"In response to infections, naive CD8 T cells give rise to effector and memory T cells. However, eliciting long-lived memory CD8 T cells remains a challenge for many infections. DNA demethylation of cytosines within CpG dinucleotides by Tet enzymes is a key epigenetic mechanism that regulates short- and long-term transcriptional programs in cells. Currently, their roles in modulating CD8 T-cell effector and memory differentiation are unclear. Here, we report that developing CD8 T cells lacking Tet1/3 preferentially differentiate into short-lived effector and effector memory cells following acute infection. Using genome-wide analyses, mice in which Tet1/3 were ablated during T-cell development and mature CD8 T cells, respectively, we show that Tet1/3 regulates these cell fates by licensing the chromatin landscape of genes downstream of T-cell receptor activation during thymic T-cell maturation. However, in mature CD8 T cells, Tet1/3 are dispensable for effector and memory cell fates. These findings unveil context-specific roles of DNA demethylation, which are essential for defining pathways that contribute to CD8 memory T-cell generation in response to infections.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2494-2518"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771685","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

Culture and its impact on research. 文化及其对研究的影响。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-22 DOI: 10.1038/s44319-025-00453-1

Frank Gannon

引用次数: 0

Structural insights into the selective recognition of RF-amide peptides by neuropeptide FF receptor 2. 神经肽FF受体对rf酰胺肽选择性识别的结构见解2。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-03-24 DOI: 10.1038/s44319-025-00428-2

Jeesoo Kim, Sooyoung Hong, Hajin Lee, Hyun Sik Lee, Chaehee Park, Jinuk Kim, Wonpil Im, Hee-Jung Choi

{"title":"Structural insights into the selective recognition of RF-amide peptides by neuropeptide FF receptor 2.","authors":"Jeesoo Kim, Sooyoung Hong, Hajin Lee, Hyun Sik Lee, Chaehee Park, Jinuk Kim, Wonpil Im, Hee-Jung Choi","doi":"10.1038/s44319-025-00428-2","DOIUrl":"10.1038/s44319-025-00428-2","url":null,"abstract":"Neuropeptide FF Receptor 2 (NPFFR2), a G-protein-coupled receptor, plays a role in pain modulation and diet-induced thermogenesis. While NPFFR2 is strongly activated by neuropeptides FF (NPFFs), it shows low activity in response to RF-amide-related peptides (RFRPs), despite the peptides belonging to a shared family. In contrast, NPFFR1, which shares high sequence similarity with NPFFR2, is activated by RFRPs and regulates reproductive hormone balance. The molecular basis for these receptor-specific interactions with their RF-amide peptides remains unclear. Here, we present cryo-electron microscopy structures of NPFFR2 in its active state bound to the agonist RF-amide peptide hNPSF, and in its ligand-free state. Structural analysis reveals that the C-terminal RF-amide moiety engages conserved residues in the transmembrane domain, while the N-terminal segment interacts in a receptor subtype-specific manner. Key selectivity-determining residues in NPFFR2 are also identified. A homology model of NPFFR1 bound to RFRP, supported by mutagenesis studies, further validates this selectivity mechanism. Additionally, structural comparison between the inactive and active states of NPFFR2 suggests a TM3-mediated activation mechanism. These findings provide insights into RF-amide peptide recognition by NPFF receptors.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2413-2434"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699924","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

Syndecans and glycosaminoglycans influence B-cell development and activation. Syndecans和糖胺聚糖影响b细胞的发育和活化。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-03-28 DOI: 10.1038/s44319-025-00432-6

Craig I McKenzie, Alexandra R Dvorscek, Zhoujie Ding, Marcus J Robinson, Kristy O'Donnell, Catherine Pitt, Daniel T Ferguson, Jesse Mulder, Marco J Herold, David M Tarlinton, Isaak Quast

{"title":"Syndecans and glycosaminoglycans influence B-cell development and activation.","authors":"Craig I McKenzie, Alexandra R Dvorscek, Zhoujie Ding, Marcus J Robinson, Kristy O'Donnell, Catherine Pitt, Daniel T Ferguson, Jesse Mulder, Marco J Herold, David M Tarlinton, Isaak Quast","doi":"10.1038/s44319-025-00432-6","DOIUrl":"10.1038/s44319-025-00432-6","url":null,"abstract":"Syndecans (SDCs) are glycosaminoglycan-containing cell surface proteins with diverse functions in the immune system with SDC1 (CD138) and SDC4 expressed in B-lineage cells. Here, we show that stem cells lacking either molecule generate fewer B-cell progenitors but give rise to mature B cells in vivo. Deletion of the plasma cell \"marker\" CD138 has no effect on homeostatic or antigen-induced plasma cell formation. Naive B cells express high SDC4 and encounter with cognate antigen results in transient CD138 upregulation and SDC4 loss, both further modulated by IL-4, IL-21, and CD40 ligation. SDC4 is downregulated on germinal center B cells and absent on most memory B cells. Glycosaminoglycans such as those attached to SDCs, and heparin, a commonly used therapeutic, regulate survival and activation of naive B cells by limiting responsiveness to cognate antigen. Conversely, ablation of SDC4 results in increased baseline and antigen-induced B-cell activation. Collectively, our data reveal B-cell activation- and subset-dependent SDC expression and show that SDC4 and GAGs can limit antigen-induced activation to promote B-cell survival and expansion.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2435-2458"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742655","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

Espin enhances confined cell migration by promoting filopodia formation and contributes to cancer metastasis. Espin通过促进丝状足形成和促进癌症转移来增强受限细胞的迁移。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-04 DOI: 10.1038/s44319-025-00437-1

Yan Wang, Peng Shi, Geyao Liu, Wei Chen, Ya-Jun Wang, Yiping Hu, Ao Yang, Tonghua Wei, Yu-Chen Chen, Ling Liang, Zheng Liu, Yan-Jun Liu, Congying Wu

{"title":"Espin enhances confined cell migration by promoting filopodia formation and contributes to cancer metastasis.","authors":"Yan Wang, Peng Shi, Geyao Liu, Wei Chen, Ya-Jun Wang, Yiping Hu, Ao Yang, Tonghua Wei, Yu-Chen Chen, Ling Liang, Zheng Liu, Yan-Jun Liu, Congying Wu","doi":"10.1038/s44319-025-00437-1","DOIUrl":"10.1038/s44319-025-00437-1","url":null,"abstract":"Genes regulating the finger-like cellular protrusions-filopodia have long been implicated in cancer metastasis. However, depleting the flat lamellipodia but retaining filopodia drastically hampers cell migration on spread surface, obscuring the role of filopodia in cell motility. It has been noticed recently that cells under confinement may employ distinct migratory machineries. However, the regulating factors have mainly been focused on cell blebbing, nuclear deformation and cell rear contractility, without much emphasis on cell protrusions and even less on filopodia. Here, by micropore-based screening, we identified espin as an active regulator for confined migration and that its overexpression was associated with metastasis. In comparison to fascin, espin showed stronger actin bundling in vitro and induced shorter and thicker filopodia in cells. Combining the imaging-compatible microchannels and DNA-based tension probes, we uncovered that espin overexpression induced excessive filopodia at the leading edge and along the sides, exerting force for confined migration. Our results demonstrate an important role for filopodia and the regulating protein-espin in confined cell migration and shed new light on cytoskeletal mechanisms underlying metastasis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2574-2596"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788028","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

Group A Streptococcal asparagine metabolism regulates bacterial virulence. A组链球菌天冬酰胺代谢调节细菌毒力。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-14 DOI: 10.1038/s44319-025-00447-z

Abhinay Sharma, Aparna Anand, Miriam Ravins, Xiaolan Zhang, Nicola Horstmann, Samuel A Shelburne, Kevin S McIver, Emanuel Hanski

{"title":"Group A Streptococcal asparagine metabolism regulates bacterial virulence.","authors":"Abhinay Sharma, Aparna Anand, Miriam Ravins, Xiaolan Zhang, Nicola Horstmann, Samuel A Shelburne, Kevin S McIver, Emanuel Hanski","doi":"10.1038/s44319-025-00447-z","DOIUrl":"10.1038/s44319-025-00447-z","url":null,"abstract":"Group A Streptococcus (GAS) causes various human diseases linked to virulome expression predominantly regulated by the two-component system (TCS), CovR/S. Here, we demonstrate that asparagine (Asn) presence in a minimal chemically defined medium increases virulence gene expression in a CovR-dependent fashion. It also decreases the transcription of asparagine synthetase (AsnA), the ABC transporter responsible for Asn uptake (GlnPQ), and that of the hemolysin toxins responsible for scavenging Asn from the host. Metabolomics data show that Asn availability increases intracellular ADP/ATP ratio, which enhances phosphatase activity in structurally related CovS sensors and is probably responsible for the Asn-mediated decrease in CovR phosphorylation. Mutants deficient in AsnA, GlnPQ, asparaginase, (AsnB) activities are attenuated in a mouse model of human GAS invasive soft tissue infection. The similarity between the mechanisms of Asn-mediated regulation of GAS virulence and tumor growth suggests that, as in cancer, components maintaining Asn homeostasis could be targeted for anti-GAS treatments.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2767-2791"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974615","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