EMBO Reports最新文献_第10页

RudLOV is an optically synchronized cargo transport method revealing unexpected effects of dynasore. RudLOV是一种光学同步的货物运输方式，显示出意想不到的王朝效应。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-02-01 Epub Date: 2024-12-10 DOI: 10.1038/s44319-024-00342-z

Tatsuya Tago, Takumi Ogawa, Yumi Goto, Kiminori Toyooka, Takuro Tojima, Akihiko Nakano, Takunori Satoh, Akiko K Satoh

{"title":"RudLOV is an optically synchronized cargo transport method revealing unexpected effects of dynasore.","authors":"Tatsuya Tago, Takumi Ogawa, Yumi Goto, Kiminori Toyooka, Takuro Tojima, Akihiko Nakano, Takunori Satoh, Akiko K Satoh","doi":"10.1038/s44319-024-00342-z","DOIUrl":"10.1038/s44319-024-00342-z","url":null,"abstract":"Live imaging of secretory cargoes is a powerful method for understanding the mechanisms of membrane trafficking. Inducing the synchronous release of cargoes from an organelle is key for enhancing microscopic observation. We developed an optical cargo-releasing method, 'retention using dark state of LOV2' (RudLOV), which enables precise spatial, temporal, and quantity control during cargo release. A limited amount of cargo-release using RudLOV is able to visualize cargo cisternal-movement and cargo-specific exit sites on the Golgi/trans-Golgi network. Moreover, by controlling the timing of cargo-release using RudLOV, we reveal the canonical and non-canonical effects of the well-known dynamin inhibitor dynasore, which inhibits early- but not late-Golgi transport and exits from the trans-Golgi network where dynamin-2 is active. Accumulation of COPI vesicles at the cis-side of the Golgi stacks in dynasore-treated cells suggests that dynasore targets COPI-uncoating/tethering/fusion machinery in the early-Golgi cisternae or endoplasmic reticulum but not in the late-Golgi cisternae. These results provide insight into the cisternal maturation of Golgi stacks.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"613-634"},"PeriodicalIF":6.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806374","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

DYRK4 upregulates antiviral innate immunity by promoting IRF3 activation. DYRK4通过促进IRF3激活来上调抗病毒先天免疫。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-02-01 Epub Date: 2024-12-19 DOI: 10.1038/s44319-024-00352-x

Xianhuang Zeng, Jiaqi Xu, Jiaqi Liu, Yang Liu, Siqi Yang, Junsong Huang, Chengpeng Fan, Mingxiong Guo, Guihong Sun

引用次数: 0

miRNA-target complementarity in cnidarians resembles its counterpart in plants. 刺胞动物中的mirna靶点互补与植物中的mirna靶点互补相似。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-02-01 Epub Date: 2025-01-02 DOI: 10.1038/s44319-024-00350-z

Yael Admoni, Arie Fridrich, Paris K Weavers, Reuven Aharoni, Talya Razin, Miguel Salinas-Saavedra, Michal Rabani, Uri Frank, Yehu Moran

{"title":"miRNA-target complementarity in cnidarians resembles its counterpart in plants.","authors":"Yael Admoni, Arie Fridrich, Paris K Weavers, Reuven Aharoni, Talya Razin, Miguel Salinas-Saavedra, Michal Rabani, Uri Frank, Yehu Moran","doi":"10.1038/s44319-024-00350-z","DOIUrl":"10.1038/s44319-024-00350-z","url":null,"abstract":"microRNAs (miRNAs) are important post-transcriptional regulators that activate silencing mechanisms by annealing to mRNA transcripts. While plant miRNAs match their targets with nearly-full complementarity leading to mRNA cleavage, miRNAs in most animals require only a short sequence called 'seed' to inhibit target translation. Recent findings showed that miRNAs in cnidarians, early-branching metazoans, act similarly to plant miRNAs, by exhibiting full complementarity and target cleavage; however, it remained unknown if seed-based regulation was possible in cnidarians. Here, we investigate the miRNA-target complementarity requirements for miRNA activity in the cnidarian Nematostella vectensis. We show that bilaterian-like complementarity of seed-only or seed and supplementary 3' matches are insufficient for miRNA-mediated knockdown. Furthermore, miRNA-target mismatches in the cleavage site decrease knockdown efficiency. Finally, miRNA silencing of a target with three seed binding sites in the 3' untranslated region that mimics typical miRNA targeting was repressed in zebrafish but not in Nematostella and another cnidarian, Hydractinia symbiolongicarpus. Altogether, these results unravel striking similarities between plant and cnidarian miRNAs supporting a possible common evolutionary origin of miRNAs in plants and animals.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"836-859"},"PeriodicalIF":6.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921065","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

RAGE is a key regulator of ductular reaction-mediated fibrosis during cholestasis. RAGE是胆汁淤积期间导管反应介导纤维化的关键调节因子。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-02-01 Epub Date: 2025-01-02 DOI: 10.1038/s44319-024-00356-7

Wai-Ling Macrina Lam, Gisela Gabernet, Tanja Poth, Melanie Sator-Schmitt, Morgana Barroso Oquendo, Bettina Kast, Sabrina Lohr, Aurora de Ponti, Lena Weiß, Martin Schneider, Dominic Helm, Karin Müller-Decker, Peter Schirmacher, Mathias Heikenwälder, Ursula Klingmüller, Doris Schneller, Fabian Geisler, Sven Nahnsen, Peter Angel

{"title":"RAGE is a key regulator of ductular reaction-mediated fibrosis during cholestasis.","authors":"Wai-Ling Macrina Lam, Gisela Gabernet, Tanja Poth, Melanie Sator-Schmitt, Morgana Barroso Oquendo, Bettina Kast, Sabrina Lohr, Aurora de Ponti, Lena Weiß, Martin Schneider, Dominic Helm, Karin Müller-Decker, Peter Schirmacher, Mathias Heikenwälder, Ursula Klingmüller, Doris Schneller, Fabian Geisler, Sven Nahnsen, Peter Angel","doi":"10.1038/s44319-024-00356-7","DOIUrl":"10.1038/s44319-024-00356-7","url":null,"abstract":"Ductular reaction (DR) is the hallmark of cholestatic diseases manifested in the proliferation of bile ductules lined by biliary epithelial cells (BECs). It is commonly associated with an increased risk of fibrosis and liver failure. The receptor for advanced glycation end products (RAGE) was identified as a critical mediator of DR during chronic injury. Yet, the direct link between RAGE-mediated DR and fibrosis as well as the mode of interaction between BECs and hepatic stellate cells (HSCs) to drive fibrosis remain elusive. Here, we delineate the specific function of RAGE on BECs during DR and its potential association with fibrosis in the context of cholestasis. Employing a biliary lineage tracing cholestatic liver injury mouse model, combined with whole transcriptome sequencing and in vitro analyses, we reveal a role for BEC-specific Rage activity in fostering a pro-fibrotic milieu. RAGE is predominantly expressed in BECs and contributes to DR. Notch ligand Jagged1 is secreted from activated BECs in a Rage-dependent manner and signals HSCs in trans, eventually enhancing fibrosis during cholestasis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"880-907"},"PeriodicalIF":6.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921113","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 dynamics of loss of heterozygosity events in genomes. 基因组中杂合性事件丢失的动力学。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-02-01 Epub Date: 2025-01-02 DOI: 10.1038/s44319-024-00353-w

Abhishek Dutta, Joseph Schacherer

引用次数: 0

Soul Men and Women-what must science do to regain public trust? 灵魂男女--科学必须做些什么才能重新赢得公众的信任？

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-20 DOI: 10.1038/s44319-024-00325-0

Arthur Caplan

引用次数: 0

Coordination of cytochrome bc₁ complex assembly at MICOS. 细胞色素bc1复合物在MICOS中的组装协调。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1038/s44319-024-00336-x

Ralf M Zerbes, Lilia Colina-Tenorio, Maria Bohnert, Karina von der Malsburg, Christian D Peikert, Carola S Mehnert, Inge Perschil, Rhena F U Klar, Rinse de Boer, Anita Kram, Ida van der Klei, Silke Oeljeklaus, Bettina Warscheid, Heike Rampelt, Martin van der Laan

{"title":"Coordination of cytochrome bc1 complex assembly at MICOS.","authors":"Ralf M Zerbes, Lilia Colina-Tenorio, Maria Bohnert, Karina von der Malsburg, Christian D Peikert, Carola S Mehnert, Inge Perschil, Rhena F U Klar, Rinse de Boer, Anita Kram, Ida van der Klei, Silke Oeljeklaus, Bettina Warscheid, Heike Rampelt, Martin van der Laan","doi":"10.1038/s44319-024-00336-x","DOIUrl":"10.1038/s44319-024-00336-x","url":null,"abstract":"The boundary and cristae domains of the mitochondrial inner membrane are connected by crista junctions. Most cristae membrane proteins are nuclear-encoded and inserted by the mitochondrial protein import machinery into the inner boundary membrane. Thus, they must overcome the diffusion barrier imposed by crista junctions to reach their final location. Here, we show that respiratory chain complexes and assembly intermediates are physically connected to the mitochondrial contact site and cristae organizing system (MICOS) that is essential for the formation and stability of crista junctions. We identify the inner membrane protein Mar26 (Fmp10) as a determinant in the biogenesis of the cytochrome bc1 complex (complex III). Mar26 couples a Rieske Fe/S protein-containing assembly intermediate to MICOS. Our data indicate that Mar26 maintains an assembly-competent Rip1 pool at crista junctions where complex III maturation likely occurs. MICOS facilitates efficient Rip1 assembly by recruiting complex III assembly intermediates to crista junctions. We propose that MICOS, via interaction with assembly factors such as Mar26, contributes to the spatial and temporal coordination of respiratory chain biogenesis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"353-384"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766600","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

Mechanisms of axoneme and centriole elimination in Naegleria gruberi. 格氏线虫轴素和中心粒消除的机制。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1038/s44319-024-00329-w

Alexander Woglar, Coralie Busso, Gabriela Garcia-Rodriguez, Friso Douma, Marie Croisier, Graham Knott, Pierre Gönczy

{"title":"Mechanisms of axoneme and centriole elimination in Naegleria gruberi.","authors":"Alexander Woglar, Coralie Busso, Gabriela Garcia-Rodriguez, Friso Douma, Marie Croisier, Graham Knott, Pierre Gönczy","doi":"10.1038/s44319-024-00329-w","DOIUrl":"10.1038/s44319-024-00329-w","url":null,"abstract":"The early branching eukaryote Naegleria gruberi can transform transiently from an amoeboid life form lacking centrioles and flagella to a flagellate life form where these elements are present, followed by reversion to the amoeboid state. The mechanisms imparting elimination of axonemes and centrioles during this reversion process are not known. Here, we uncover that flagella primarily fold onto the cell surface and fuse within milliseconds with the plasma membrane. Once internalized, axonemes are severed by Spastin into similarly-sized fragments that are then enclosed by membranes, before their contents are eliminated through the lysosomal pathway. Moreover, we discovered that centrioles undergo progressive K63 autophagy-linked poly-ubiquitination and K48 proteasome-promoting poly-ubiquitination, and that such ubiquitination occurs next to centriolar microtubules. Most centrioles are eliminated in either lysosomes or the cytoplasm in a lysosomal- and proteasome-dependent manner. Strikingly, we uncover in addition that centrioles can be shed in the extracellular milieu and taken up by other cells. Collectively, these findings reveal fundamental mechanisms governing the elimination of essential cellular constituents in Naegleria that may operate broadly in eukaryotic systems.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"385-406"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766893","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

Gpr54 deletion accelerates hair cycle and hair regeneration. Gpr54 基因缺失可加速毛发周期和毛发再生。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-25 DOI: 10.1038/s44319-024-00327-y

Weili Xia, Caibing Wang, Biao Guo, Zexin Tang, Xiyun Ye, Yongyan Dang

{"title":"Gpr54 deletion accelerates hair cycle and hair regeneration.","authors":"Weili Xia, Caibing Wang, Biao Guo, Zexin Tang, Xiyun Ye, Yongyan Dang","doi":"10.1038/s44319-024-00327-y","DOIUrl":"10.1038/s44319-024-00327-y","url":null,"abstract":"GPR54, or KiSS-1R (Kisspeptin receptor), is key in puberty initiation and tumor metastasis prevention, but its role on hair follicles remains unclear. Our study shows that Gpr54 knockout (KO) accelerates hair cycle, synchronized hair regeneration and transplanted hair growth in mice. In Gpr54 KO mice, DPC (dermal papilla cell) activity is enhanced, with elevated expression of Wnts, VEGF, and IGF-1, which stimulate HFSCs. Gpr54 deletion also raises the number of CD34+ and Lgr5+ HFSCs. The Gpr54 inhibitor, kisspeptin234, promotes hair shaft growth in cultured mouse hair follicles and boosts synchronized hair regeneration in vivo. Mechanistically, Gpr54 deletion suppresses NFATC3 expression in DPCs and HFSCs, and decreases levels of SFRP1, a Wnt inhibitor. It also activates the Wnt/β-catenin pathway, promoting β-catenin nuclear localization and upregulating target genes such as Lef1 and ALP. Our findings suggest that Gpr54 deletion may accelerate the hair cycle and promote hair regeneration in mice by regulating the NAFTc3-SFRP1-Wnt signaling pathway. These findings suggest that Gpr54 could be a possible target for future hair loss treatments.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"200-217"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715675","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

Local translatome sustains synaptic function in impaired Wallerian degeneration. 在沃勒里变性受损的情况下，局部转译体能维持突触功能。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-10-31 DOI: 10.1038/s44319-024-00301-8

Maria Paglione, Leonardo Restivo, Sarah Zakhia, Arnau Llobet Rosell, Marco Terenzio, Lukas J Neukomm

{"title":"Local translatome sustains synaptic function in impaired Wallerian degeneration.","authors":"Maria Paglione, Leonardo Restivo, Sarah Zakhia, Arnau Llobet Rosell, Marco Terenzio, Lukas J Neukomm","doi":"10.1038/s44319-024-00301-8","DOIUrl":"10.1038/s44319-024-00301-8","url":null,"abstract":"After injury, severed axons separated from their somas activate programmed axon degeneration, a conserved pathway to initiate their degeneration within a day. Conversely, severed projections deficient in programmed axon degeneration remain morphologically preserved with functional synapses for weeks to months after axotomy. How this synaptic function is sustained remains currently unknown. Here, we show that dNmnat overexpression attenuates programmed axon degeneration in distinct neuronal populations. Severed projections remain morphologically preserved for weeks. When evoked, they elicit a postsynaptic behavior, a readout for preserved synaptic function. We used ribosomal pulldown to isolate the translatome from these projections 1 week after axotomy. Translatome candidates of enriched biological classes identified by transcriptional profiling are validated in a screen using a novel automated system to detect evoked antennal grooming as a proxy for preserved synaptic function. RNAi-mediated knockdown reveals that transcripts of the mTORC1 pathway, a mediator of protein synthesis, and of candidate genes involved in protein ubiquitination and Ca2+ homeostasis are required for preserved synaptic function. Our translatome dataset also uncovers several uncharacterized Drosophila genes associated with human disease. It may offer insights into novel avenues for therapeutic treatments.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"61-83"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557441","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