EMBO Reports最新文献_第4页

Epicardial VEGFC/D signaling is essential for coronary lymphangiogenesis.

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-24 DOI: 10.1038/s44319-025-00431-7

Ester de la Cruz, Vanessa Cadenas, Susana Temiño, Guillermo Oliver, Miguel Torres

引用次数: 0

Structural insights into the selective recognition of RF-amide peptides by neuropeptide FF receptor 2.

IF 6.5 1区生物学

EMBO Reports Pub 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":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lack of AtMC1 catalytic activity triggers autoimmunity dependent on NLR stability. 缺乏 AtMC1 催化活性会引发依赖于 NLR 稳定性的自身免疫。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-20 DOI: 10.1038/s44319-025-00426-4

Jose Salguero-Linares, Laia Armengot, Joel Ayet, Nerea Ruiz-Solaní, Svenja C Saile, Marta Salas-Gómez, Esperanza Fernandez, Lode Denolf, Fernando Navarrete, Jenna Krumbach, Markus Kaiser, Simon Stael, Frank Van Breusegem, Kris Gevaert, Farnusch Kaschani, Morten Petersen, Farid El Kasmi, Marc Valls, Núria S Coll

{"title":"Lack of AtMC1 catalytic activity triggers autoimmunity dependent on NLR stability.","authors":"Jose Salguero-Linares, Laia Armengot, Joel Ayet, Nerea Ruiz-Solaní, Svenja C Saile, Marta Salas-Gómez, Esperanza Fernandez, Lode Denolf, Fernando Navarrete, Jenna Krumbach, Markus Kaiser, Simon Stael, Frank Van Breusegem, Kris Gevaert, Farnusch Kaschani, Morten Petersen, Farid El Kasmi, Marc Valls, Núria S Coll","doi":"10.1038/s44319-025-00426-4","DOIUrl":"https://doi.org/10.1038/s44319-025-00426-4","url":null,"abstract":"Plants utilize cell surface-localized pattern recognition receptors (PRRs) and intracellular nucleotide-binding leucine-rich repeat (NLR) receptors to detect non-self and elicit robust immune responses. Fine-tuning the homeostasis of these receptors is critical to prevent their hyperactivation. Here, we show that Arabidopsis plants lacking metacaspase 1 (AtMC1) display autoimmunity dependent on immune signalling components downstream of NLR and PRR activation. Overexpression of a catalytically inactive AtMC1 in an atmc1 background triggers severe autoimmunity partially dependent on the same immune signalling components. Overexpression of the E3 ligase SNIPER1, a master regulator of NLR homeostasis, fully reverts the AtMC1-dependent autoimmunity phenotype, inferring that a broad defect in NLR turnover may underlie the severe phenotype observed. Catalytically inactive AtMC1 localizes to punctate structures that are degraded through autophagy. Considering also previous evidence on the proteostatic functions of AtMC1, we speculate that Wt AtMC1 may either directly or indirectly control NLR protein levels, thereby preventing autoimmunity.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669185","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

Liquid-liquid phase separation of LARP7 restrains HIV-1 replication. LARP7 的液-液相分离抑制了 HIV-1 的复制。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-20 DOI: 10.1038/s44319-025-00421-9

Zhuoxin Li, Xiya Fang, Bing Zhao, Ran Liu, Yezhuang Shen, Tingting Li, Yining Wang, Zenglin Guo, Wen Wang, Biyu Zhang, Qiuying Han, Xin Xu, Kai Wang, Libing Yin, Weili Gong, Ailing Li, Tao Zhou, Teng Li, Weihua Li

引用次数: 0

tRNA lysidinylation is essential for the minimal translation system in the Plasmodium falciparum apicoplast.

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-20 DOI: 10.1038/s44319-025-00420-w

Rubayet Elahi, Sean T Prigge

{"title":"tRNA lysidinylation is essential for the minimal translation system in the Plasmodium falciparum apicoplast.","authors":"Rubayet Elahi, Sean T Prigge","doi":"10.1038/s44319-025-00420-w","DOIUrl":"10.1038/s44319-025-00420-w","url":null,"abstract":"For decades, researchers have sought to define minimal translation systems to uncover fundamental principles of life and advance biotechnology. tRNAs, essential components of this machinery, decode mRNA codons into amino acids. The apicoplast of malaria parasites contains 25 tRNA isotypes in its organellar genome-the lowest number found in known translation systems. Efficient translation in such minimal systems depends heavily on post-transcriptional tRNA modifications. One such modification, lysidine at the wobble position (C34) of tRNACAU, distinguishes between methionine (AUG) and isoleucine (AUA) codons. tRNA isoleucine lysidine synthetase (TilS) produces lysidine, which is nearly ubiquitous in bacteria and essential for cellular viability. Here, we report a TilS ortholog (PfTilS) targeted to the apicoplast of Plasmodium falciparum. We demonstrate that PfTilS activity is essential for parasite survival and apicoplast function, likely due to its role in protein translation. This study is the first to characterize TilS in an endosymbiotic organelle, contributing to research on eukaryotic organelles and minimal translational systems. Moreover, the absence of lysidine in humans highlights a potential target for antimalarial strategies.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669293","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

Sertm2 is a conserved micropeptide that promotes GDNF-mediated motor neuron subtype specification.

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-19 DOI: 10.1038/s44319-025-00400-0

Fang-Yu Hsu, Ya-Ping Yen, Hung-Chi Fan, Mien Chang, Jun-An Chen

{"title":"Sertm2 is a conserved micropeptide that promotes GDNF-mediated motor neuron subtype specification.","authors":"Fang-Yu Hsu, Ya-Ping Yen, Hung-Chi Fan, Mien Chang, Jun-An Chen","doi":"10.1038/s44319-025-00400-0","DOIUrl":"https://doi.org/10.1038/s44319-025-00400-0","url":null,"abstract":"Small open-reading frame-encoded micropeptides within long noncoding RNAs (lncRNAs) are often overlooked due to their small size and low abundance. However, emerging evidence links these micropeptides to various biological pathways, though their roles in neural development and neurodegeneration remain unclear. Here, we investigate the function of murine micropeptide Sertm2, encoded by the lncRNA A730046J19Rik, during spinal motor neuron (MN) development. Sertm2 is predicted to be a conserved transmembrane protein found in both mouse and human, with subcellular analysis revealing that it is enriched in the cytoplasm and neurites. By generating C terminally Flag-tagged Sertm2 and expressing it from the A730046J19Rik locus, we demonstrate that the Sertm2 micropeptide localizes in spinal MNs in mice. The GDNF signaling-induced Etv4+ motor pool is impaired in Sertm2 knockout mice, which display motor nerve arborization defects that culminate in impaired motor coordination and muscle weakness. Similarly, human SERTM2 knockout iPSC-derived MNs also display reduced ETV4+ motor pools, highlighting that Sertm2 is a novel, evolutionarily conserved micropeptide essential for maintaining GDNF-induced MN subtype identity.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663009","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

Root stem cell homeostasis in Arabidopsis involves cell-type specific transcription factor complexes.

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-19 DOI: 10.1038/s44319-025-00422-8

Vivien I Strotmann, Monica L García-Gómez, Yvonne Stahl

{"title":"Root stem cell homeostasis in Arabidopsis involves cell-type specific transcription factor complexes.","authors":"Vivien I Strotmann, Monica L García-Gómez, Yvonne Stahl","doi":"10.1038/s44319-025-00422-8","DOIUrl":"https://doi.org/10.1038/s44319-025-00422-8","url":null,"abstract":"In Arabidopsis thaliana the root stem cell niche (SCN) is maintained by a complex regulatory network crucial for growth and developmental plasticity. However, many aspects of this network, particularly concerning stem cell quiescence and replenishment, remain unclear. Here, we investigate the interactions of key transcription factors (TFs) BRASSINOSTEROID AT VASCULAR AND ORGANIZING CENTRE (BRAVO), PLETHORA 3 (PLT3), and WUSCHEL-RELATED HOMEOBOX 5 (WOX5) in SCN maintenance. Analysis of mutants reveals their combinatorial regulation of cell fates and divisions in the SCN. In addition, studies using Fluorescence Resonance Energy Transfer Fluorescence Lifetime Imaging Microscopy (FRET-FLIM) in combination with novel analysis methods enable us to quantify protein-protein interaction (PPI) affinities and higher-order complex formation among these TFs. Our findings were integrated into a computational model, indicating that cell-type specific protein complex profiles and formations, influenced by prion-like domains in PLT3, play an important role in regulating the SCN. We propose that these unique protein complex signatures may serve as indicators of cell specificity, enriching the regulatory network that governs stem cell maintenance and replenishment in the Arabidopsis root.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663008","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

SERTM2: a neuroactive player in the world of micropeptides.

IF 6.5 1区生物学

EMBO Reports Pub 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

Borrelia burgdorferi lacking all cp32 prophage plasmids retains full infectivity in mice.

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-03-19 DOI: 10.1038/s44319-025-00378-9

Chad Hillman, Hannah Theriault, Anton Dmitriev, Satyender Hansra, Patricia A Rosa, Jenny Wachter

引用次数: 0

Developmental mitochondrial complex I activity determines lifespan.

IF 6.5 1区生物学

EMBO Reports Pub 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":"https://doi.org/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":""},"PeriodicalIF":6.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0