EMBO Reports最新文献_第10页

Molecular architecture of glideosome and nuclear F-actin in Plasmodium falciparum. 恶性疟原虫滑体和核f -肌动蛋白的分子结构。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-24 DOI: 10.1038/s44319-025-00415-7

Vojtěch Pražák, Daven Vasishtan, Kay Grünewald, Ross G Douglas, Josie L Ferreira

{"title":"Molecular architecture of glideosome and nuclear F-actin in Plasmodium falciparum.","authors":"Vojtěch Pražák, Daven Vasishtan, Kay Grünewald, Ross G Douglas, Josie L Ferreira","doi":"10.1038/s44319-025-00415-7","DOIUrl":"10.1038/s44319-025-00415-7","url":null,"abstract":"Actin-based motility is required for the transmission of malaria sporozoites. While this has been shown biochemically, filamentous actin has remained elusive and has not been directly visualised inside the parasite. Using focused ion beam milling and electron cryo-tomography, we studied dynamic actin filaments in unperturbed Plasmodium falciparum cells for the first time. This allowed us to dissect the assembly, path and fate of actin filaments during parasite gliding and determine a complete 3D model of F-actin within sporozoites. We observe micrometre long actin filaments, much longer than expected from in vitro studies. After their assembly at the parasite's apical end, actin filaments continue to grow as they are transported down the cell as part of the glideosome machinery, and are disassembled at the basal end in a rate-limiting step. Large pores in the IMC, constrained to the basal end, may facilitate actin exchange between the pellicular space and cytosol for recycling and maintenance of directional flow. The data also reveal striking actin bundles in the nucleus. Implications for motility and transmission are discussed.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1984-1996"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12019134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699923","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

GEF14 acts as a specific activator of the plant osmotic signaling pathway by controlling ROP6 nanodomain formation. GEF14通过控制ROP6纳米结构域的形成，作为植物渗透信号通路的特异性激活剂。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-13 DOI: 10.1038/s44319-025-00412-w

Lucille Gorgues, Marija Smokvarska, Caroline Mercier, Clara P Igisch, Amandine Crabos, Armelle Dongois, Vincent Bayle, Jean-Bernard Fiche, Philippe Nacry, Marcelo Nollmann, Yvon Jaillais, Alexandre Martinière

{"title":"GEF14 acts as a specific activator of the plant osmotic signaling pathway by controlling ROP6 nanodomain formation.","authors":"Lucille Gorgues, Marija Smokvarska, Caroline Mercier, Clara P Igisch, Amandine Crabos, Armelle Dongois, Vincent Bayle, Jean-Bernard Fiche, Philippe Nacry, Marcelo Nollmann, Yvon Jaillais, Alexandre Martinière","doi":"10.1038/s44319-025-00412-w","DOIUrl":"10.1038/s44319-025-00412-w","url":null,"abstract":"During their growth, plants encounter and respond to a variety of environmental signals. However, the mechanisms underlying the integration and specificity of signals remain poorly understood. Rho of Plant (ROP) signaling plays a central role in various processes, including polar cell growth and responses to different stimuli, and relies on stimuli-dependent membrane nanodomains. The effector composition of ROP6 nanodomains varies depending on the signal and may be involved in downstream signal specificity. In this study, we explore how ROP6 signaling is regulated by Guanine nucleotide Exchange Factor (GEF) during osmotic stress. We find that GEF14 is required for osmotically induced ROS accumulation. This isoform acts specifically in response to osmotic stimulation, since it is dispensable for other stimuli. We demonstrate that GEF14 activates ROP6 and controls its clustering in a signal-specific manner. Furthermore, we find that GEF14 relocates from the cytoplasm to clusters at the plasma membrane after osmotic stimulation. Together, our results suggest that a single GEF isoform can encode for signal specificity controlling ROP6 activation, clustering and downstream cellular responses.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2146-2165"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12019552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623992","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

MIA40 suppresses cell death induced by apoptosis-inducing factor 1. MIA40抑制凋亡诱导因子1诱导的细胞死亡。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1038/s44319-025-00406-8

Ben Hur Marins Mussulini, Klaudia K Maruszczak, Piotr Draczkowski, Mayra A Borrero-Landazabal, Selvaraj Ayyamperumal, Artur Wnorowski, Michal Wasilewski, Agnieszka Chacinska

{"title":"MIA40 suppresses cell death induced by apoptosis-inducing factor 1.","authors":"Ben Hur Marins Mussulini, Klaudia K Maruszczak, Piotr Draczkowski, Mayra A Borrero-Landazabal, Selvaraj Ayyamperumal, Artur Wnorowski, Michal Wasilewski, Agnieszka Chacinska","doi":"10.1038/s44319-025-00406-8","DOIUrl":"10.1038/s44319-025-00406-8","url":null,"abstract":"Mitochondria harbor respiratory complexes that perform oxidative phosphorylation. Complex I is the first enzyme of the respiratory chain that oxidizes NADH. A dysfunction in complex I can result in higher cellular levels of NADH, which in turn strengthens the interaction between apoptosis-inducing factor 1 (AIFM1) and Mitochondrial intermembrane space import and assembly protein 40 (MIA40) in the mitochondrial intermembrane space. We investigated whether MIA40 modulates the activity of AIFM1 upon increased NADH/NAD+ balance. We found that in model cells characterized by an increase in NADH the AIFM1-MIA40 interaction is strengthened and these cells demonstrate resistance to AIFM1-induced cell death. Either silencing of MIA40, rescue of complex I, or depletion of NADH through the expression of yeast NADH-ubiquinone oxidoreductase-2 sensitized NDUFA13-KO cells to AIFM1-induced cell death. These findings indicate that the complex of MIA40 and AIFM1 suppresses AIFM1-induced cell death in a NADH-dependent manner. This study identifies an effector complex involved in regulating the programmed cell death that accommodates the metabolic changes in the cell and provides a molecular explanation for AIFM1-mediated chemoresistance of cancer cells.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1835-1862"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585192","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

Autocrine Wingless constricts the Drosophila embryonic gut by Ca⁺²-mediated repolarisation of mesoderm cells. 自分泌无翅通过Ca+2介导的中胚层细胞重极化收缩果蝇胚胎肠。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1038/s44319-025-00411-x

Delia Ricolo, Francesca Tamba, Jordi Casanova

{"title":"Autocrine Wingless constricts the Drosophila embryonic gut by Ca+2-mediated repolarisation of mesoderm cells.","authors":"Delia Ricolo, Francesca Tamba, Jordi Casanova","doi":"10.1038/s44319-025-00411-x","DOIUrl":"10.1038/s44319-025-00411-x","url":null,"abstract":"Wg/Wnt signalling-a highly conserved transduction pathway-has most commonly been found to be involved in patterning, cell fate, or cell proliferation, but less so in shaping organs or body parts. A remarkable case of the latter is the role of Wg signalling in the midgut of the Drosophila embryo. The Drosophila embryonic midgut is divided into four chambers that arise by the formation of three constrictions at distinct sites along the midgut. In particular, Wg is responsible for the middle constriction, a role first described more than 30 years ago. However, while some partial data have been obtained regarding the formation of this gut constriction, an overall picture of the process is lacking. Here we unveil that Wg signalling leads to this constriction by inducing ClC-a transcription in a subset of mesodermal cells. ClC-a, encodes a chloride channel, which in turn prompts a Ca+2 pulse in these cells. Consequently, the mesoderm cells, which already showed some polarity, repolarise and in so doing so they reshape the microtubule organisation, therefore inducing the constriction of the cells.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1737-1748"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585191","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

Transdifferentiation of plasmatocytes to crystal cells in the lymph gland of Drosophila melanogaster. 黑腹果蝇淋巴浆细胞向晶体细胞的转分化。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-12 DOI: 10.1038/s44319-025-00366-z

Julien Marcetteau, Patrícia Duarte, Alexandre B Leitão, Élio Sucena

{"title":"Transdifferentiation of plasmatocytes to crystal cells in the lymph gland of Drosophila melanogaster.","authors":"Julien Marcetteau, Patrícia Duarte, Alexandre B Leitão, Élio Sucena","doi":"10.1038/s44319-025-00366-z","DOIUrl":"10.1038/s44319-025-00366-z","url":null,"abstract":"Under homeostatic conditions, haematopoiesis in Drosophila larvae occurs in the lymph gland and sessile haemocyte clusters to produce two functionally and morphologically different cells: plasmatocytes and crystal cells. It is well-established that in the lymph gland both cell types stem from a binary decision of the medullary prohaemocyte precursors. However, in sessile clusters and dorsal vessel, crystal cells have been shown to originate from the transdifferentiation of plasmatocytes in a Notch/Serrate-dependent manner. We show that transdifferentiation occurs also in the lymph gland. In vivo phagocytosis assays confirm that cortical plasmatocytes are functionally differentiated phagocytic cells. We uncover a double-positive population in the cortical zone that lineage-tracing and long-term live imaging experiments show will differentiate into crystal cells. The reduction of Notch levels within the lymph gland plasmatocyte population reduces crystal cell number. This extension of a transdifferentiation mechanism reinforces the growing role of haematopoietic plasticity in maintaining homeostasis in Drosophila and vertebrate systems. Future work should test the regulation and relative contribution of these two processes under different immunological and/or metabolic conditions.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2077-2097"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12019564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613962","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

Cytosolic CRISPR RNAs for efficient application of RNA-targeting CRISPR-Cas systems. 有效应用 RNA 靶向 CRISPR-Cas 系统的细胞膜 CRISPR RNA。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-02-26 DOI: 10.1038/s44319-025-00399-4

Ezra C K Cheng, Joe K C Lam, S Chul Kwon

{"title":"Cytosolic CRISPR RNAs for efficient application of RNA-targeting CRISPR-Cas systems.","authors":"Ezra C K Cheng, Joe K C Lam, S Chul Kwon","doi":"10.1038/s44319-025-00399-4","DOIUrl":"10.1038/s44319-025-00399-4","url":null,"abstract":"Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) technologies have evolved rapidly over the past decade with the continuous discovery of new Cas systems. In particular, RNA-targeting CRISPR-Cas13 proteins are promising single-effector systems to regulate target mRNAs without altering genomic DNA, yet the current Cas13 systems are restrained by suboptimal efficiencies. Here, we show that U1 promoter-driven CRISPR RNAs (crRNAs) increase the efficiency of various applications, including RNA knockdown and editing, without modifying the Cas13 protein effector. We confirm that U1-driven crRNAs are exported into the cytoplasm, while conventional U6 promoter-driven crRNAs are mostly confined to the nucleus. Furthermore, we reveal that the end positions of crRNAs expressed by the U1 promoter are consistent regardless of guide sequences and lengths. We also demonstrate that U1-driven crRNAs, but not U6-driven crRNAs, can efficiently repress the translation of target genes in combination with catalytically inactive Cas13 proteins. Finally, we show that U1-driven crRNAs can counteract the inhibitory effect of miRNAs. Our simple and effective engineering enables unprecedented cytosolic RNA-targeting applications.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1891-1912"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515024","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

Developmental mitochondrial complex I activity determines lifespan. 发育线粒体复合体I的活性决定了寿命。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-17 DOI: 10.1038/s44319-025-00416-6

Rhoda Stefanatos, Fiona Robertson, Beatriz Castejon-Vega, Yizhou Yu, Alejandro Huerta Uribe, Kevin Myers, Tetsushi Kataura, Viktor I Korolchuk, Oliver D K Maddocks, L Miguel Martins, Alberto Sanz

{"title":"Developmental mitochondrial complex I activity determines lifespan.","authors":"Rhoda Stefanatos, Fiona Robertson, Beatriz Castejon-Vega, Yizhou Yu, Alejandro Huerta Uribe, Kevin Myers, Tetsushi Kataura, Viktor I Korolchuk, Oliver D K Maddocks, L Miguel Martins, Alberto Sanz","doi":"10.1038/s44319-025-00416-6","DOIUrl":"10.1038/s44319-025-00416-6","url":null,"abstract":"Aberrant mitochondrial function has been associated with an increasingly large number of human disease states. Observations from in vivo models where mitochondrial function is altered suggest that maladaptations to mitochondrial dysfunction may underpin disease pathology. We hypothesized that the severity of this maladaptation could be shaped by the plasticity of the system when mitochondrial dysfunction manifests. To investigate this, we have used inducible fly models of mitochondrial complex I (CI) dysfunction to reduce mitochondrial function at two stages of the fly lifecycle, from early development and adult eclosion. Here, we show that in early life (developmental) mitochondrial dysfunction results in severe reductions in survival and stress resistance in adulthood, while flies where mitochondrial function is perturbed from adulthood, are long-lived and stress resistant despite having up to a 75% reduction in CI activity. After excluding developmental defects as a cause, we went on to molecularly characterize these two populations of mitochondrially compromised flies, short- and long-lived. We find that our short-lived flies have unique transcriptomic, proteomic and metabolomic responses, which overlap significantly in discrete models of CI dysfunction. Our data demonstrate that early mitochondrial dysfunction via CI depletion elicits a maladaptive response, which severely reduces survival, while CI depletion from adulthood is insufficient to reduce survival and stress resistance.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1957-1983"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12019323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647653","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

SERTM2: a neuroactive player in the world of micropeptides. SERTM2：微肽世界中的神经活性参与者。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-19 DOI: 10.1038/s44319-025-00404-w

Michela Lisi, Tiziana Santini, Tiziano D'Andrea, Beatrice Salvatori, Adriano Setti, Alessandro Paiardini, Sofia Nutarelli, Carmine Nicoletti, Flaminia Pellegrini, Sergio Fucile, Irene Bozzoni, Julie Martone

引用次数: 0

Regulating stem cell-based embryo model research in Japan : Proposals, debates, and future directions. 调控日本干细胞胚胎模型研究：建议、争论和未来方向。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-14 DOI: 10.1038/s44319-025-00409-5

Tsutomu Sawai, Shu Ishida, Chie Kobayashi, Yasuna Murase, Gyo Nakao, Tomonori Nakamura, Julian Savulescu

引用次数: 0

Auditory fear memory retrieval requires BLA-LS and LS-VMH circuitries via GABAergic and dopaminergic neurons. 听觉恐惧记忆提取需要通过gaba能和多巴胺能神经元的BLA-LS和LS-VMH回路。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1038/s44319-025-00403-x

Miao Chen, Jun Li, Weiran Shan, Jianjun Yang, Zhiyi Zuo

{"title":"Auditory fear memory retrieval requires BLA-LS and LS-VMH circuitries via GABAergic and dopaminergic neurons.","authors":"Miao Chen, Jun Li, Weiran Shan, Jianjun Yang, Zhiyi Zuo","doi":"10.1038/s44319-025-00403-x","DOIUrl":"10.1038/s44319-025-00403-x","url":null,"abstract":"Fear and associated learning and memory are critical for developing defensive behavior. Excessive fear and anxiety are important components of post-traumatic stress disorder. However, the neurobiology of fear conditioning, especially tone-related fear memory retrieval, has not been clearly defined, which limits specific intervention development for patients with excessive fear and anxiety. Here, we show that auditory fear memory retrieval stimuli activate multiple brain regions including the lateral septum (LS). Inhibition of the LS and the connection between basolateral amygdala (BLA) and LS or between LS and ventromedial nucleus of the hypothalamus (VMH) attenuates tone-related fear conditioning and memory retrieval. Inhibiting GABAergic neurons or dopaminergic neurons in the LS also attenuates tone-related fear conditioning. Our data further show that fear conditioning is inhibited by blocking orexin B signaling in the LS. Our results indicate that the neural circuitries BLA-LS and LS-VMH are critical for tone-related fear conditioning and memory retrieval, and that GABAergic neurons, dopaminergic neurons and orexin signaling in the LS participate in this auditory fear conditioning.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1816-1834"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585190","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