EMBO Reports最新文献_第5页

Mechanisms of cilia regeneration in Xenopus multiciliated epithelium in vivo. 章鱼体内多纤毛上皮细胞的纤毛再生机制

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-14 DOI: 10.1038/s44319-025-00414-8

Venkatramanan G Rao, Vignesh A Subramanianbalachandar, Magdalena M Magaj, Stefanie Redemann, Saurabh S Kulkarni

{"title":"Mechanisms of cilia regeneration in Xenopus multiciliated epithelium in vivo.","authors":"Venkatramanan G Rao, Vignesh A Subramanianbalachandar, Magdalena M Magaj, Stefanie Redemann, Saurabh S Kulkarni","doi":"10.1038/s44319-025-00414-8","DOIUrl":"10.1038/s44319-025-00414-8","url":null,"abstract":"Cilia regeneration is a physiological event, and while studied extensively in unicellular organisms, it remains poorly understood in vertebrates. In this study, using Xenopus multiciliated cells (MCCs), we demonstrate that, unlike unicellular organisms, deciliation removes the transition zone (TZ) and the ciliary axoneme. While MCCs immediately begin regenerating the axoneme, surprisingly, the TZ assembly is delayed. However, ciliary tip proteins, Sentan and Clamp, localize to regenerating cilia without delay. Using cycloheximide (CHX) to block protein synthesis, we show that the TZ protein B9d1 is not present in the cilia precursor pool and requires new transcription/translation, providing insights into the delayed repair of TZ. Moreover, MCCs in CHX treatment assemble fewer but near wild-type length cilia by gradually concentrating ciliogenesis proteins like IFTs at a few basal bodies. Using mathematical modeling, we show that cilia length, compared to cilia number, has a larger influence on the force generated by MCCs. Our results question the requirement of TZ in motile cilia assembly and provide insights into the fundamental question of how cells determine organelle size and number.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633573","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

GEF14 acts as a specific activator of the plant osmotic signaling pathway by controlling ROP6 nanodomain formation.

IF 6.5 1区生物学

EMBO Reports Pub 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":"https://doi.org/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":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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.

IF 6.5 1区生物学

EMBO Reports Pub 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":"https://doi.org/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":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deficiency of neuronal LGR4 increases energy expenditure and inhibits food intake via hypothalamic leptin signaling.

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-11 DOI: 10.1038/s44319-025-00398-5

Liping Zhang, Yuan Li, Wenbin Gao, Ziru Li, Tong Wu, Chunhui Lang, Liangyou Rui, Weizhen Zhang

{"title":"Deficiency of neuronal LGR4 increases energy expenditure and inhibits food intake via hypothalamic leptin signaling.","authors":"Liping Zhang, Yuan Li, Wenbin Gao, Ziru Li, Tong Wu, Chunhui Lang, Liangyou Rui, Weizhen Zhang","doi":"10.1038/s44319-025-00398-5","DOIUrl":"https://doi.org/10.1038/s44319-025-00398-5","url":null,"abstract":"The metabolic effects of leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) remain largely unknown. Here, we showed that knockdown of Lgr4 in nestin progenitor or Sp1 mature neurons reduced high fat diet (HFD)-induced obesity by increasing energy expenditure and inhibiting food intake. Deficiency of LGR4 in AgRP neurons increased energy expenditure, and inhibited food intake, leading to alterations in glucose and lipid metabolism. Knock-down of Lgr4 in Sf1 neurons enhanced energy expenditure, reduced adiposity, and improved glucose and lipid metabolism. The metabolic benefits of neuronal LGR4 occurred via improvement of leptin signaling in AgRP and Sf1 neurons. Knockdown of Lgr4 in nestin, Sp1, AgRP or Sf1 neurons decreased hypothalamic levels of SOCS-3, and increased phosphorylation of STAT3. These alterations were associated with a significant reduction in the hypothalamic levels of β-catenin. Inhibition of β-catenin signaling by Dkk1 significantly attenuated the decrement of phospho-STAT3 and concurrent increase of SOCS-3 induced by Rspondin 3, an endogenous ligand for LGR4. Our results thus demonstrate that hypothalamic LGR4 may promote energy conversation by increasing food intake and decreasing energy expenditure. Deficiency of neuronal LGR4 improves hypothalamic leptin sensitivity via suppression of β-catenin signaling.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604341","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

miR-708-5p is elevated in bipolar patients and can induce mood disorder-associated behavior in mice.

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-10 DOI: 10.1038/s44319-025-00410-y

Carlotta Gilardi, Helena C Martins, Brunno Rocha Levone, Alessandra Lo Bianco, Silvia Bicker, Pierre-Luc Germain, Fridolin Gross, Ayse Özge Sungur, Theresa M Kisko, Frederike Stein, Susanne Meinert, Rainer K W Schwarting, Markus Wöhr, Udo Dannlowski, Tilo Kircher, Gerhard Schratt

{"title":"miR-708-5p is elevated in bipolar patients and can induce mood disorder-associated behavior in mice.","authors":"Carlotta Gilardi, Helena C Martins, Brunno Rocha Levone, Alessandra Lo Bianco, Silvia Bicker, Pierre-Luc Germain, Fridolin Gross, Ayse Özge Sungur, Theresa M Kisko, Frederike Stein, Susanne Meinert, Rainer K W Schwarting, Markus Wöhr, Udo Dannlowski, Tilo Kircher, Gerhard Schratt","doi":"10.1038/s44319-025-00410-y","DOIUrl":"https://doi.org/10.1038/s44319-025-00410-y","url":null,"abstract":"Mood disorders (MDs) are caused by an interplay of genetic and environmental (GxE) risk factors. However, molecular pathways engaged by GxE risk factors are poorly understood. Using small-RNA sequencing in peripheral blood mononuclear cells (PBMCs), we show that the bipolar disorder (BD)-associated microRNA miR-708-5p is upregulated in healthy human subjects with a high genetic or environmental predisposition for MDs. miR-708-5p is further upregulated in the hippocampus of rats which underwent juvenile social isolation, a model of early life stress. Hippocampal overexpression of miR-708-5p in adult male mice is sufficient to elicit MD-associated behavioral endophenotypes. We further show that miR-708-5p directly targets Neuronatin (Nnat), an endoplasmic reticulum protein. Restoring Nnat expression in the hippocampus of miR-708-5p-overexpressing mice rescues miR-708-5p-dependent behavioral phenotypes. Finally, miR-708-5p is upregulated in PBMCs from patients diagnosed with MD. Peripheral miR-708-5p expression allows to differentiate male BD patients from patients suffering from major depressive disorder (MDD). In summary, we describe a potential functional role for the miR-708-5p/Nnat pathway in MD etiology and identify miR-708-5p as a potential biomarker for the differential diagnosis of MDs.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596584","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

SH3KBP1 promotes skeletal myofiber formation and functionality through ER/SR architecture integrity.

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-10 DOI: 10.1038/s44319-025-00413-9

Alexandre Guiraud, Nathalie Couturier, Emilie Christin, Léa Castellano, Marine Daura, Carole Kretz-Remy, Alexandre Janin, Alireza Ghasemizadeh, Peggy Del Carmine, Laloe Monteiro, Ludivine Rotard, Colline Sanchez, Vincent Jacquemond, Claire Burny, Stéphane Janczarski, Anne-Cécile Durieux, David Arnould, Norma Beatriz Romero, Mai Thao Bui, Vladimir L Buchman, Laura Julien, Marc Bitoun, Vincent Gache

{"title":"SH3KBP1 promotes skeletal myofiber formation and functionality through ER/SR architecture integrity.","authors":"Alexandre Guiraud, Nathalie Couturier, Emilie Christin, Léa Castellano, Marine Daura, Carole Kretz-Remy, Alexandre Janin, Alireza Ghasemizadeh, Peggy Del Carmine, Laloe Monteiro, Ludivine Rotard, Colline Sanchez, Vincent Jacquemond, Claire Burny, Stéphane Janczarski, Anne-Cécile Durieux, David Arnould, Norma Beatriz Romero, Mai Thao Bui, Vladimir L Buchman, Laura Julien, Marc Bitoun, Vincent Gache","doi":"10.1038/s44319-025-00413-9","DOIUrl":"https://doi.org/10.1038/s44319-025-00413-9","url":null,"abstract":"Dynamic changes in the arrangement of myonuclei and the organization of the sarcoplasmic reticulum are important determinants of myofiber formation and muscle function. To find factors associated with muscle integrity, we perform an siRNA screen and identify SH3KBP1 as a new factor controlling myoblast fusion, myonuclear positioning, and myotube elongation. We find that the N-terminus of SH3KBP1 binds to dynamin-2 while the C-terminus associates with the endoplasmic reticulum through calnexin, which in turn control myonuclei dynamics and ER integrity, respectively. Additionally, in mature muscle fibers, SH3KBP1 contributes to the formation of triads and modulates the Excitation-Contraction Coupling process efficiency. In Dnm2R465W/+ mice, a model for centronuclear myopathy (CNM), depletion of Sh3kbp1 expression aggravates CNM-related atrophic phenotypes and impaired autophagic flux in mutant skeletal muscle fiber. Altogether, our results identify SH3KBP1 as a new regulator of myofiber integrity and function.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596588","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

Type-2 innate signals are dispensable for skeletal muscle regeneration and pathology linked to Duchenne muscular dystrophy.

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-01 Epub Date: 2025-02-03 DOI: 10.1038/s44319-025-00383-y

Melina Messing, Marine Theret, Michael R Hughes, Jiaqi Wu, Omar Husain Syed, Fang Fang Li, Yicong Li, Fabio M V Rossi, Kelly M McNagny

{"title":"Type-2 innate signals are dispensable for skeletal muscle regeneration and pathology linked to Duchenne muscular dystrophy.","authors":"Melina Messing, Marine Theret, Michael R Hughes, Jiaqi Wu, Omar Husain Syed, Fang Fang Li, Yicong Li, Fabio M V Rossi, Kelly M McNagny","doi":"10.1038/s44319-025-00383-y","DOIUrl":"10.1038/s44319-025-00383-y","url":null,"abstract":"Immune responses play an integral role in skeletal muscle regeneration. In the genetically inherited muscle disease Duchenne muscular dystrophy (DMD), muscle regeneration is disrupted, leading to chronic inflammation, fibrosis, and early mortality. Previously, it has been suggested that type-2 innate immune cells, particularly eosinophils and their production of IL-4, play an essential role in effective muscle regeneration after acute injury. We here re-investigate the role of eosinophils in skeletal muscle repair using mice deficient in eosinophils (ΔdblGATA), or deficient in IL-4R/IL-13R signaling through STAT6 (Stat6-/-). We show that neither deficiency has an impact on skeletal muscle regeneration in response to acute injury as quantified by fiber size, immune cell infiltration, or muscle-resident stem cell proliferation. We also investigate the role of STAT6 signaling in mdx:Stat6-/- mice, a model of DMD and, again, find that ablation of STAT6 signaling has no effect on the rate or severity of fibrotic scar formation or disease progression. In contrast to previous models, our data suggest a negligible role for eosinophils and STAT6 signaling in skeletal muscle regeneration after acute or chronic injury.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1406-1421"},"PeriodicalIF":6.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122456","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

Next-generation biotechnology inspired by extremes : The potential of extremophile organisms for synthetic biology and for more efficient and sustainable biotechnology.

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-01 Epub Date: 2025-02-27 DOI: 10.1038/s44319-025-00389-6

Shuang Zheng, Mingwei Shao, Wanze Wang, Guo-Qiang Chen

引用次数: 0

A CRISPR-Cas9 screen reveals genetic determinants of the cellular response to decitabine.

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-01 Epub Date: 2025-02-10 DOI: 10.1038/s44319-025-00385-w

Pinqi Zhang, Zhuqiang Zhang, Yiyi Wang, Wenlong Du, Xingrui Song, Weiyi Lai, Hailin Wang, Bing Zhu, Jun Xiong

{"title":"A CRISPR-Cas9 screen reveals genetic determinants of the cellular response to decitabine.","authors":"Pinqi Zhang, Zhuqiang Zhang, Yiyi Wang, Wenlong Du, Xingrui Song, Weiyi Lai, Hailin Wang, Bing Zhu, Jun Xiong","doi":"10.1038/s44319-025-00385-w","DOIUrl":"10.1038/s44319-025-00385-w","url":null,"abstract":"Decitabine (DAC), a well-recognized DNA hypomethylating agent, has been applied to treat acute myeloid leukemia. However, clinic investigations revealed that DNA methylation reduction does not correlate with a clinical response, and relapse is prevalent. To gain a better understanding of its anti-tumor mechanism, we perform a temporally resolved CRISPR-Cas9 screen to identify factors governing the DAC response. We show that DNA damage generated by DNMT-DNA adducts and 5-aza-dUTP misincorporation through the dCMP deaminase DCTD act as drivers of DAC-induced acute cytotoxicity. The DNA damage that arises during the next S phase is dependent on DNA replication, unveiling a trans-cell cycle effect of DAC on genome stability. By exploring candidates for synthetic lethality, we unexpectedly uncover that KDM1A promotes survival after DAC treatment through interactions with ZMYM3 and CoREST, independent of its demethylase activity or regulation of viral mimicry. These findings emphasize the importance of DNA repair pathways in DAC response and provide potential biomarkers.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1528-1565"},"PeriodicalIF":6.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390512","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

Exonuclease action of replicative polymerase gamma drives damage-induced mitochondrial DNA clearance.

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-01 Epub Date: 2025-01-31 DOI: 10.1038/s44319-025-00380-1

Akshaya Seshadri, Anjana Badrinarayanan

引用次数: 0