The EMBO Journal最新文献

Microtubule pushing and cortical pulling cooperate to orient and position the mitotic spindle 微管的推动和皮质的拉动共同决定有丝分裂纺锤体的方向和位置

The EMBO Journal Pub Date : 2026-10-17 DOI: 10.1038/s44318-026-00937-3

Alikhan Yeltokov,Tara M Finegan,Alexander G Fletcher,Sabrina Ghadaouia,Holly E Lovegrove,Dan T Bergstralh

{"title":"Microtubule pushing and cortical pulling cooperate to orient and position the mitotic spindle","authors":"Alikhan Yeltokov,Tara M Finegan,Alexander G Fletcher,Sabrina Ghadaouia,Holly E Lovegrove,Dan T Bergstralh","doi":"10.1038/s44318-026-00937-3","DOIUrl":"https://doi.org/10.1038/s44318-026-00937-3","url":null,"abstract":"Abstract While regulation of spindle positioning and orientation is known to be mediated by cortical pulling forces generated by dynein on astral microtubules, the contribution of microtubule-based pushing forces remains less clear. We developed a two-dimensional computational model that incorporates both cortical pulling and microtubule pushing to examine spindle behavior across diverse cell types and geometries. The model successfully recapitulates experimental observations in cells that round during mitosis, including Drosophila follicular epithelial cells, Drosophila neuroblasts, and the early C. elegans embryo. Our analysis shows that pulling forces are the dominant determinants of directional spindle orientation. However, pushing forces play essential supporting roles by preventing spindle stalling, enhancing robustness, and facilitating efficient alignment. We further applied our model to irregularly shaped zebrafish endothelial cells, which exhibit complex, non-spherical geometries and dynamic morphology. In this context, our model demonstrates that asymmetric distributions of cortical force generators, potentially enriched at cell–cell junctions, are sufficient to explain off-center spindle positioning. Together, this work establishes a unified framework linking cell geometry, molecular polarity cues, and force balance to spindle dynamics.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209873","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

Expression patterns of CD24 and CD27 resolve the origins and gradual differentiation of CD11c+ atypical memory B-cells after malaria infection CD24和CD27的表达模式决定了疟疾感染后CD11c+非典型记忆b细胞的起源和逐渐分化

The EMBO Journal Pub Date : 2026-10-11 DOI: 10.1038/s44318-026-00941-7

Alan-Dine Courey-Ghaouzi,Linn Kleberg,Zaynab Mousavian,Maximilian Julius Lautenbach,Marta Pirronello,Ganesh E Phad,Mattias N E Forsell,Anna Färnert,Christopher Sundling

{"title":"Expression patterns of CD24 and CD27 resolve the origins and gradual differentiation of CD11c+ atypical memory B-cells after malaria infection","authors":"Alan-Dine Courey-Ghaouzi,Linn Kleberg,Zaynab Mousavian,Maximilian Julius Lautenbach,Marta Pirronello,Ganesh E Phad,Mattias N E Forsell,Anna Färnert,Christopher Sundling","doi":"10.1038/s44318-026-00941-7","DOIUrl":"https://doi.org/10.1038/s44318-026-00941-7","url":null,"abstract":"Abstract Atypical B-cells (ABCs) are observed across infections, yet their ontogeny and differentiation remain unclear. Using high-dimensional flow cytometry, single-cell transcriptomics, V(D)J sequencing, and functional assays in samples from individuals with malaria and healthy donors, we identify markers of cellular origin while tracking ABC differentiation. Early ABCs express CD11c and arise predominantly from memory B-cells. Two intermediate states originate from germinal center-derived and marginal zone-like B-cells. Pseudotime and lineage analyses reveal trajectories marked by progressive loss of CD24 and CD27, which is recapitulated in vitro, defining bona fide differentiation programs. Differentiation culminates in late ABCs lacking CD24, CD27, and CD21, while expressing CD11c, T-bet, and NKG7 at high levels, exhibiting partial overlap with double-negative-2 B-cells. Early and intermediate stages show greater plasma-cell differentiation potential and cytokine production capacity, whereas later stages acquire transcriptomic signatures of antigen presentation and association with microbial particles, defining stage-dependent functions that reconcile conflicting ABC roles. Comparable ABC populations occur in healthy blood and tonsils, with tissue-associated class switching and CD86 expression consistent with recent T-cell interaction. This framework consolidates ABC definitions along a single differentiation axis and clarifies their cellular origins.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149151546","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

Dynamics of bicoid mRNA localisation and translation dictate morphogen gradient formation bicoid mRNA定位和翻译的动态决定了形态梯度的形成

The EMBO Journal Pub Date : 2026-10-10 DOI: 10.1038/s44318-026-00927-5

Thamarailingam Athilingam,Elise L Wilby,Pierre Bensidoun,Antonio Trullo,Morgane Verbrugghe,Jérémy Dufourt,Xingzhu Shi,Mounia Lagha,Timothy E Saunders,Timothy T Weil

{"title":"Dynamics of bicoid mRNA localisation and translation dictate morphogen gradient formation","authors":"Thamarailingam Athilingam,Elise L Wilby,Pierre Bensidoun,Antonio Trullo,Morgane Verbrugghe,Jérémy Dufourt,Xingzhu Shi,Mounia Lagha,Timothy E Saunders,Timothy T Weil","doi":"10.1038/s44318-026-00927-5","DOIUrl":"https://doi.org/10.1038/s44318-026-00927-5","url":null,"abstract":"Abstract The transcription factor Bicoid (Bcd) protein guides early Drosophila patterning and is the best-characterised morphogen. The source of the morphogen, bcd mRNA, is maternally deposited during oogenesis and localised to the anterior pole. When and where Bcd protein is produced and how this protein gradient is dynamically shaped remains contentious. Here, we use the SunTag reporter system to quantitatively examine the spatiotemporal profile of bcd mRNA translation in vivo. We show that association with Processing bodies (P bodies) in mature oocytes prevent premature bcd mRNA translation. Following egg activation, bcd mRNA dissociates from P bodies and translation is observed at the anterior pole. Translation remains largely restricted to the anterior domain throughout early development. At cellularisation, translation ceases and the remaining bcd mRNA associates with reformed P bodies, which appear to block any further translation. We use these observations to create a new modified synthesis-diffusion-degradation model of Bcd gradient, which is consistent with experimental measurements. Overall, our study reveals that bcd mRNA translation is tightly controlled in space and time during oogenesis and early embryogenesis.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149151089","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

Switch from canonical to recombination-dependent DNA synthesis by M-CDK phosphorylation of DNA Polα 通过DNA Polα的M-CDK磷酸化，从典型到重组依赖的DNA合成切换

The EMBO Journal Pub Date : 2026-10-10 DOI: 10.1038/s44318-026-00919-5

Juan de Dios Barba Tena,Riccardo Montecchi,Maxime Lambert,Thomas Defrance,Elisabeth Gueydon,Julie Petit,Marjorie Drac,Noémie Legoff,Michela Galli,Isabelle Goiffon,Thierry Gostan,Khadija El Koulali,Serge Urbach,David Toczyski,Nicolas Talarek,Etienne Schwob

{"title":"Switch from canonical to recombination-dependent DNA synthesis by M-CDK phosphorylation of DNA Polα","authors":"Juan de Dios Barba Tena,Riccardo Montecchi,Maxime Lambert,Thomas Defrance,Elisabeth Gueydon,Julie Petit,Marjorie Drac,Noémie Legoff,Michela Galli,Isabelle Goiffon,Thierry Gostan,Khadija El Koulali,Serge Urbach,David Toczyski,Nicolas Talarek,Etienne Schwob","doi":"10.1038/s44318-026-00919-5","DOIUrl":"https://doi.org/10.1038/s44318-026-00919-5","url":null,"abstract":"Abstract Cells preserve genome stability while occasionally generating genetic diversity through mutations and chromosomal rearrangements, but how these opposing outcomes are balanced remains unclear. Because late-replicating regions evolve more rapidly, we investigated the consequences of reduced origin licensing and lengthened S phase in yeast. Under these conditions, cells progress slowly through S phase without checkpoint activation, and enter mitosis with under-replicated DNA. We show that mitotic cyclin-dependent kinase (M-CDK) phosphorylates DNA polymerase α (Pol α), displacing it from replication forks and triggering fork collapse at mitotic entry. The resulting DNA damage response provides a window for mitotic DNA synthesis (MiDAS), enabling completion of replication through error-prone, recombination-dependent mechanisms resembling break-induced replication (BIR) and Fork Stalling & Template Switching (FoSTeS). These findings identify Pol α as a critical M-CDK target that promotes the transition from canonical replication to recombination-driven DNA synthesis when cells enter mitosis with incompletely-duplicated chromosomes. This mechanism offers a potential explanation for the accelerated evolution of late-replicating genomic regions.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149151090","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

The miR-744-5p/connexin 43 axis modulates Salmonella-containing vacuole association with the Golgi network miR-744-5p/连接蛋白43轴调节含沙门氏菌液泡与高尔基网络的关联

The EMBO Journal Pub Date : 2026-10-10 DOI: 10.1038/s44318-026-00929-3

Jane Dias,Caio Haddad Franco,Laura Maria Alcantara,Susana Costa,Miguel Mano,Ana Eulalio

{"title":"The miR-744-5p/connexin 43 axis modulates Salmonella-containing vacuole association with the Golgi network","authors":"Jane Dias,Caio Haddad Franco,Laura Maria Alcantara,Susana Costa,Miguel Mano,Ana Eulalio","doi":"10.1038/s44318-026-00929-3","DOIUrl":"https://doi.org/10.1038/s44318-026-00929-3","url":null,"abstract":"Abstract MicroRNAs are increasingly recognised as important regulators of host–pathogen interactions. Using a large-scale functional screening approach, we identified miR-744-5p as a strong inhibitor of Salmonella infection. Time-course analyses in epithelial cells revealed that miR-744-5p moderately restricts early infection but exerts a much stronger inhibitory effect on late intracellular replication. This activity is conserved across Salmonella strains of distinct sequence types, whereas inhibition of Shigella flexneri is limited to early infection stages. Integrated transcriptomic analyses identified connexin 43 as a functionally relevant miR-744-5p target. Connexin 43 expression is strongly upregulated during Salmonella infection, and functional studies demonstrated that connexin 43 depletion selectively impaired late-stage intracellular replication, while CRISPRa-mediated connexin 43 upregulation enhanced bacterial proliferation. Notably, this function was independent of the canonical gap junction intercellular communication. Mechanistically, connexin 43 is required to maintain Golgi network organisation, enabling proper positioning of the Salmonella -containing vacuole. Thus, infection-induced downregulation of miR-744-5p promotes connexin 43 expression to support the formation of a permissive vacuolar replicative niche, revealing an unanticipated role for connexin 43 in Golgi homeostasis.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"73 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149151091","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 senescence: six decades of discovery and reinvention 细胞衰老：六十年的发现和改造

The EMBO Journal Pub Date : 2026-10-02 DOI: 10.1038/s44318-026-00922-w

Myrthe Klaver,Lotte Sophie Steeneken,Naomi Veeningen,Abdullah Altulea,Marco Demaria

{"title":"Cellular senescence: six decades of discovery and reinvention","authors":"Myrthe Klaver,Lotte Sophie Steeneken,Naomi Veeningen,Abdullah Altulea,Marco Demaria","doi":"10.1038/s44318-026-00922-w","DOIUrl":"https://doi.org/10.1038/s44318-026-00922-w","url":null,"abstract":"Abstract Cellular senescence has undergone a remarkable conceptual evolution since its discovery in 1961. Initially described by Hayflick and Moorhead as the finite proliferative lifespan of cultured human cells, senescence was first viewed as a consequence of cellular aging. The identification of telomere shortening, senescence biomarkers, and oncogene- and damage-induced senescence subsequently established its molecular basis and role as a tumor-suppressive stress response. The discovery of the senescence-associated secretory phenotype (SASP) further transformed the field by revealing that senescent cells actively communicate with and remodel their tissue environment. Genetic mouse models later demonstrated causal roles for senescent cells in tissue repair, aging, and age-related disease, while senotherapeutics established senescence as a therapeutic target. Here, we trace the major conceptual transitions that shaped the field, from replicative endpoint to stress-response program, regulator of tissue homeostasis, driver of chronic pathology, and clinically actionable process. We discuss the discoveries, controversies, and technological advances underlying these transitions and how emerging single-cell technologies, precision biomarkers, and targeted interventions are shaping the next era of senescence research.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090206","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

A dual-action bacteriophage protein Ped1 degrades DNA and blocks replication in Pseudomonas aeruginosa 双作用噬菌体蛋白Ped1降解DNA并阻断铜绿假单胞菌的复制

The EMBO Journal Pub Date : 2026-10-02 DOI: 10.1038/s44318-026-00924-8

Tietao Wang,Wenbo Yan,Chenchen Wang,Longgang Sang,Yingxin Yang,Jingru Zhao,Chao Li,Lijun Liu,Yani Zhang,Shuai Le,Haihua Liang

{"title":"A dual-action bacteriophage protein Ped1 degrades DNA and blocks replication in Pseudomonas aeruginosa","authors":"Tietao Wang,Wenbo Yan,Chenchen Wang,Longgang Sang,Yingxin Yang,Jingru Zhao,Chao Li,Lijun Liu,Yani Zhang,Shuai Le,Haihua Liang","doi":"10.1038/s44318-026-00924-8","DOIUrl":"https://doi.org/10.1038/s44318-026-00924-8","url":null,"abstract":"Abstract To fully harness phage therapy against escalating antimicrobial resistance, it is imperative to elucidate the fundamental mechanisms by which viruses systematically dismantle host physiology. In this study, we identify Ped1, a protein from Pseudomonas aeruginosa phage PaoP5, which suppresses bacterial growth through two mechanisms: degradation of genomic DNA and direct inhibition of the replication machinery. Our 2.3-Å crystal structure and biochemical profiling reveal that Ped1 adopts a previously uncharacterized α/β-nuclease architecture, enabling the efficient cleavage of both double-stranded and single-stranded DNA. Furthermore, we demonstrate that Ped1 physically interacts with the host replicative helicase, DnaB, to suppress its activity during DNA replication. Reciprocally, DnaB binds Ped1 to neutralize its nuclease function, acting as an internal immunity partner. Evolutionary analysis indicates that Ped1 is a lineage-specific toxin strictly conserved among Pseudomonas phages. Collectively, this work identifies a novel, dual-function phage effector that coordinately disrupts genomic integrity and replication fidelity, thus advancing our understanding of the phage–host molecular arms race, and describing a promising scaffold for the development of next-generation antimicrobials against multidrug-resistant P. aeruginosa .","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090226","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

A conserved archaeal protein with evolutionary links to bacterial ribosome hibernation and eukaryotic energy sensing 一种保守的古细菌蛋白，与细菌核糖体冬眠和真核生物能量感应有进化联系

The EMBO Journal Pub Date : 2026-10-02 DOI: 10.1038/s44318-026-00918-6

Diorge P Souza,Mira B May,Jackson Carrion,Vikram Alva,Alex Bisson,Joseph H Davis

{"title":"A conserved archaeal protein with evolutionary links to bacterial ribosome hibernation and eukaryotic energy sensing","authors":"Diorge P Souza,Mira B May,Jackson Carrion,Vikram Alva,Alex Bisson,Joseph H Davis","doi":"10.1038/s44318-026-00918-6","DOIUrl":"https://doi.org/10.1038/s44318-026-00918-6","url":null,"abstract":"Abstract Ribosome hibernation helps cells survive stress by reversibly silencing translation and preserving ribosomal complexes. Although well characterized in bacteria and eukaryotes, archaeal hibernation remains poorly understood. Using cryoEM of archaeal lysates, we identified AHA ( A MPKγ- H PF from A rchaea), a broadly conserved ribosome-associated factor composed of two modules. AHA bound across ribosomal subunits, occluding the mRNA channel and tRNA binding sites, supporting its role in ribosome hibernation. ΔAHA cells displayed reduced viability, loss of ribosomal proteins in the stationary phase, and impaired growth reentry in rich media. Phylogenetic analyses revealed that AHA’s C-terminal domain is homologous to the bacterial Hibernation Promoting Factor (HPF), consistent with inheritance from the last universal common ancestor and thereby identifying HPF as a universal hibernation module in prokaryotes. Strikingly, we observed two AMP molecules bound to AHA’s N-terminal CBS-tetrad, which showed both sequence and structural similarity to the eukaryotic energy sensor AMPKγ, supporting a shared evolutionary origin of the archaeal CBS-tetrad and the AMPKγ family. Together, these findings uncover a widespread archaeal ribosome hibernation factor and reveal an evolutionary connection between prokaryotic ribosomal hibernation and eukaryotic energy sensing.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090223","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

Leptin-sensitive hypothalamic Lepr+/Glp1r+ neurons limit hyperphagia and weight gain in diet-induced obesity 瘦素敏感的下丘脑Lepr+/Glp1r+神经元限制饮食性肥胖的贪食和体重增加

The EMBO Journal Pub Date : 2026-10-02 DOI: 10.1038/s44318-026-00914-w

Dylan M Belmont-Rausch,Benedicte Schultz Kapel,Abigail J Tomlinson,Chao Ding,Allison M Duensing,Bernd Coester,Cecilie Vad Mathiesen,Leonie Cabot,Jenny M Brown,Charlotte Høy Kruse,Shad Hassan,Elizabeth Heaton,Christoffer Clemmensen,Michael W Schwartz,Henning Fenselau,Martin G Myers,Tune H Pers

{"title":"Leptin-sensitive hypothalamic Lepr+/Glp1r+ neurons limit hyperphagia and weight gain in diet-induced obesity","authors":"Dylan M Belmont-Rausch,Benedicte Schultz Kapel,Abigail J Tomlinson,Chao Ding,Allison M Duensing,Bernd Coester,Cecilie Vad Mathiesen,Leonie Cabot,Jenny M Brown,Charlotte Høy Kruse,Shad Hassan,Elizabeth Heaton,Christoffer Clemmensen,Michael W Schwartz,Henning Fenselau,Martin G Myers,Tune H Pers","doi":"10.1038/s44318-026-00914-w","DOIUrl":"https://doi.org/10.1038/s44318-026-00914-w","url":null,"abstract":"Abstract Despite loss of responsiveness to exogenous leptin in obesity, endogenous leptin continues to restrain feeding, although the neural substrates that remain sensitive and mediate this effect remain unknown. Combining spatial transcriptomics with single-nucleus RNA sequencing in mice with diet-induced obesity (DIO), we here show that while most hypothalamic leptin receptor ( Lepr )-positive neurons minimally respond to elevated leptin, a single subpopulation defined by glucagon-like peptide-1 receptor ( Glp1r ) co-expression retains robust leptin sensitivity. These Lepr + /Glp1r + neurons project onto and inhibit orexigenic Agrp neurons. Lepr deletion from Lepr + /Glp1r + neurons blocks the anorectic effect of exogenous leptin, reinstates hyperphagic responses normally suppressed in DIO, amplifies the obesogenic response to palatable diet, and unexpectedly attenuates hypothalamic microglial activation – a hallmark of DIO previously attributed to diet rather than leptin signaling. Hence, preserved leptin responses by a single neuronal population in the hypothalamus limit hyperphagia and weight gain, among other responses, during obesity.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"125 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090224","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

Clustering of host N-glycans by the microneme MIC1/4/6 complex licenses Toxoplasma rhoptry discharge MIC1/4/6复合体对宿主n -聚糖的聚集使弓形虫得以释放

The EMBO Journal Pub Date : 2026-09-25 DOI: 10.1038/s44318-026-00911-z

Dylan Valleau,Mudita Goyal,Justin M Roberts,Frances Male,Gary E Ward,Sebastian Lourido

{"title":"Clustering of host N-glycans by the microneme MIC1/4/6 complex licenses Toxoplasma rhoptry discharge","authors":"Dylan Valleau,Mudita Goyal,Justin M Roberts,Frances Male,Gary E Ward,Sebastian Lourido","doi":"10.1038/s44318-026-00911-z","DOIUrl":"https://doi.org/10.1038/s44318-026-00911-z","url":null,"abstract":"Abstract To initiate the process of invasion, apicomplexan parasites must discharge the contents of specialized organelles called rhoptries into host cells. This process requires prior recognition and binding of the host cell by proteins released from another set of parasite organelles, the micronemes. However, the host–parasite interactions required for rhoptry discharge are largely unknown. Here, we performed a host cell-directed genome-wide screen for factors that mediate rhoptry discharge from Toxoplasma gondii , the causative agent of toxoplasmosis. The screen identified host N-glycosylation and cholesterol biosynthesis as pathways required for normal rhoptry discharge. A trimeric microneme complex, MIC1/4/6, interfaces with both pathways by binding host N-glycans to cluster proteins in a process dependent on host plasma membrane cholesterol. The process can be inhibited by depletion of host cholesterol or competition with exogenous glycans. This clustering of host factors by MIC1/4/6 likely prepares the host membrane for rhoptry discharge, delineating a new step in the Toxoplasma invasion process.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049731","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