EMBO Journal最新文献_第3页

MCTS2 and distinct eIF2D roles in uORF-dependent translation regulation revealed by in vitro re-initiation assays.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-02 DOI: 10.1038/s44318-024-00347-3

Romane Meurs, Mara De Matos, Adrian Bothe, Nicolas Guex, Tobias Weber, Aurelio A Teleman, Nenad Ban, David Gatfield

{"title":"MCTS2 and distinct eIF2D roles in uORF-dependent translation regulation revealed by in vitro re-initiation assays.","authors":"Romane Meurs, Mara De Matos, Adrian Bothe, Nicolas Guex, Tobias Weber, Aurelio A Teleman, Nenad Ban, David Gatfield","doi":"10.1038/s44318-024-00347-3","DOIUrl":"https://doi.org/10.1038/s44318-024-00347-3","url":null,"abstract":"Ribosomes scanning from the mRNA 5' cap to the start codon may initiate at upstream open reading frames (uORFs), decreasing protein biosynthesis. Termination at a uORF can lead to re-initiation, where 40S subunits resume scanning and initiate another translation event downstream. The noncanonical translation factors MCTS1-DENR participate in re-initiation at specific uORFs, but knowledge of other trans-acting factors or uORF features influencing re-initiation is limited. Here, we establish a cell-free re-initiation assay using HeLa lysates to address this question. Comparing in vivo and in vitro re-initiation on uORF-containing reporters, we validate MCTS1-DENR-dependent re-initiation in vitro. Using this system and ribosome profiling in cells, we found that knockdown of the MCTS1-DENR homolog eIF2D causes widespread gene deregulation unrelated to uORF translation, and thus distinct to MCTS1-DENR-dependent re-initiation regulation. Additionally, we identified MCTS2, encoded by an Mcts1 retrogene, as a DENR partner promoting re-initiation in vitro, providing a plausible explanation for clinical differences associated with DENR vs. MCTS1 mutations in humans.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923906","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

FOXP1 phosphorylation antagonizes its O-GlcNAcylation in regulating ATR activation in response to replication stress.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1038/s44318-024-00323-x

Xuefei Zhu, Congwen Gao, Bin Peng, Jingwei Xue, Donghui Xia, Liu Yang, Jiexiang Zhang, Xinrui Gao, Yilin Hu, Shixian Lin, Peng Gong, Xingzhi Xu

引用次数: 0

Towards routine proteome profiling of FFPE tissue: insights from a 1,220-case pan-cancer study. 实现 FFPE 组织的常规蛋白质组分析：一项 1220 例泛癌症研究的启示。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1038/s44318-024-00289-w

Johanna Tüshaus, Stephan Eckert, Marius Schliemann, Yuxiang Zhou, Pauline Pfeiffer, Christiane Halves, Federico Fusco, Johannes Weigel, Lisa Hönikl, Vicki Butenschön, Rumyana Todorova, Hilka Rauert-Wunderlich, Matthew The, Andreas Rosenwald, Volker Heinemann, Julian Holch, Katja Steiger, Claire Delbridge, Bernhard Meyer, Wilko Weichert, Carolin Mogler, Peer-Hendrik Kuhn, Bernhard Kuster

{"title":"Towards routine proteome profiling of FFPE tissue: insights from a 1,220-case pan-cancer study.","authors":"Johanna Tüshaus, Stephan Eckert, Marius Schliemann, Yuxiang Zhou, Pauline Pfeiffer, Christiane Halves, Federico Fusco, Johannes Weigel, Lisa Hönikl, Vicki Butenschön, Rumyana Todorova, Hilka Rauert-Wunderlich, Matthew The, Andreas Rosenwald, Volker Heinemann, Julian Holch, Katja Steiger, Claire Delbridge, Bernhard Meyer, Wilko Weichert, Carolin Mogler, Peer-Hendrik Kuhn, Bernhard Kuster","doi":"10.1038/s44318-024-00289-w","DOIUrl":"10.1038/s44318-024-00289-w","url":null,"abstract":"Proteome profiling of formalin-fixed paraffin-embedded (FFPE) specimens has gained traction for the analysis of cancer tissue for the discovery of molecular biomarkers. However, reports so far focused on single cancer entities, comprised relatively few cases and did not assess the long-term performance of experimental workflows. In this study, we analyze 1220 tumors from six cancer entities processed over the course of three years. Key findings include the need for a new normalization method ensuring equal and reproducible sample loading for LC-MS/MS analysis across cohorts, showing that tumors can, on average, be profiled to a depth of >4000 proteins and discovering that current software fails to process such large ion mobility-based online fractionated datasets. We report the first comprehensive pan-cancer proteome expression resource for FFPE material comprising 11,000 proteins which is of immediate utility to the scientific community, and can be explored via a web resource. It enables a range of analyses including quantitative comparisons of proteins between patients and cohorts, the discovery of protein fingerprints representing the tissue of origin or proteins enriched in certain cancer entities.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"304-329"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669710","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

In vivo HIV-1 nuclear condensates safeguard against cGAS and license reverse transcription.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1038/s44318-024-00316-w

Selen Ay, Julien Burlaud-Gaillard, Anastasia Gazi, Yevgeniy Tatirovsky, Celine Cuche, Jean-Sebastien Diana, Viviana Scoca, James P Di Santo, Philippe Roingeard, Fabrizio Mammano, Francesca Di Nunzio

{"title":"In vivo HIV-1 nuclear condensates safeguard against cGAS and license reverse transcription.","authors":"Selen Ay, Julien Burlaud-Gaillard, Anastasia Gazi, Yevgeniy Tatirovsky, Celine Cuche, Jean-Sebastien Diana, Viviana Scoca, James P Di Santo, Philippe Roingeard, Fabrizio Mammano, Francesca Di Nunzio","doi":"10.1038/s44318-024-00316-w","DOIUrl":"10.1038/s44318-024-00316-w","url":null,"abstract":"Entry of viral capsids into the nucleus induces the formation of biomolecular condensates called HIV-1 membraneless organelles (HIV-1-MLOs). Several questions remain about their persistence, in vivo formation, composition, and function. Our study reveals that HIV-1-MLOs persisted for several weeks in infected cells, and their abundance correlated with viral infectivity. Using an appropriate animal model, we show that HIV-1-MLOs were formed in vivo during acute infection. To explore the viral structures present within these biomolecular condensates, we used a combination of double immunogold labeling, electron microscopy and tomography, and unveiled a diverse array of viral core structures. Our functional analyses showed that HIV-1-MLOs remained stable during treatment with a reverse transcriptase inhibitor, maintaining the virus in a dormant state. Drug withdrawal restored reverse transcription, promoting efficient virus replication akin to that observed in latently infected patients on antiretroviral therapy. However, when HIV-1 MLOs were deliberately disassembled by pharmacological treatment, we observed a complete loss of viral infectivity. Our findings show that HIV-1 MLOs shield the final reverse transcription product from host immune detection.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"166-199"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774568","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

SNARE mimicry by the CD225 domain of IFITM3 enables regulation of homotypic late endosome fusion.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-12-09 DOI: 10.1038/s44318-024-00334-8

Kazi Rahman, Isaiah Wilt, Abigail A Jolley, Bhabadeb Chowdhury, Siddhartha A K Datta, Alex A Compton

{"title":"SNARE mimicry by the CD225 domain of IFITM3 enables regulation of homotypic late endosome fusion.","authors":"Kazi Rahman, Isaiah Wilt, Abigail A Jolley, Bhabadeb Chowdhury, Siddhartha A K Datta, Alex A Compton","doi":"10.1038/s44318-024-00334-8","DOIUrl":"10.1038/s44318-024-00334-8","url":null,"abstract":"The CD225/Dispanin superfamily contains membrane proteins that regulate vesicular transport and membrane fusion events required for neurotransmission, glucose transport, and antiviral immunity. However, how the CD225 domain controls membrane trafficking has remained unknown. Here we show that the CD225 domain contains a SNARE-like motif that enables interaction with cellular SNARE fusogens. Proline-rich transmembrane protein 2 (PRRT2) encodes a SNARE-like motif that enables interaction with neuronal SNARE proteins; mutations in this region disrupt SNARE binding and are linked to neurological disease. Another CD225 member, interferon-induced transmembrane protein 3 (IFITM3), protects cells against influenza A virus infection. IFITM3 interacts with SNARE proteins that mediate late endosome-late endosome (homotypic) fusion and late endosome-lysosome (heterotypic) fusion. IFITM3 binds to syntaxin 7 (STX7) in cells and in vitro, and mutations that abrogate STX7 binding cause loss of antiviral activity against influenza A virus. Mechanistically, IFITM3 disrupts assembly of the SNARE complex controlling homotypic fusion and accelerates the trafficking of endosomal cargo to lysosomes. Our results suggest that SNARE modulation plays a previously unrecognized role in the diverse functions performed by CD225 proteins.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"534-562"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803274","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

An EpCAM/Trop2 mechanostat differentially regulates collective behaviour of human carcinoma cells. EpCAM/Trop2机械调节器可对人类癌细胞的集体行为进行不同程度的调节。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-21 DOI: 10.1038/s44318-024-00309-9

Azam Aslemarz, Marie Fagotto-Kaufmann, Artur Ruppel, Christine Fagotto-Kaufmann, Martial Balland, Paul Lasko, François Fagotto

{"title":"An EpCAM/Trop2 mechanostat differentially regulates collective behaviour of human carcinoma cells.","authors":"Azam Aslemarz, Marie Fagotto-Kaufmann, Artur Ruppel, Christine Fagotto-Kaufmann, Martial Balland, Paul Lasko, François Fagotto","doi":"10.1038/s44318-024-00309-9","DOIUrl":"10.1038/s44318-024-00309-9","url":null,"abstract":"EpCAM and its close relative Trop2 are well-known cell surface markers of carcinoma, but their potential role in cancer metastasis remains unclear. They are known, however, to downregulate myosin-dependent contractility, a key parameter involved in adhesion and migration. We investigate here the morphogenetic impact of the high EpCAM and Trop2 levels typically found in epithelial breast cancer cells, using spheroids of MCF7 cells as an in vitro model. Intriguingly, EpCAM depletion stimulated spheroid cohesive spreading, while Trop2 depletion had the opposite effect. Combining cell biological and biophysical approaches, we demonstrate that while EpCAM and Trop2 both contribute to moderate cell contractility, their depletions differentially impact on the process of \"wetting\" a substrate, here both matrix and neighboring cells, by affecting the balance of cortical tension at cell and tissue interfaces. These distinct phenotypes can be explained by partial enrichment at specific interfaces. Our data are consistent with the EpCAM-Trop2 pair acting as a mechanostat that tunes adhesive and migratory behaviours.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"75-106"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689445","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

How J-chain ensures the assembly of immunoglobulin IgM pentamers.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-12-04 DOI: 10.1038/s44318-024-00317-9

Chiara Giannone, Xenia Mess, Ruiming He, Maria Rita Chelazzi, Annika Mayer, Anush Bakunts, Tuan Nguyen, Yevheniia Bushman, Andrea Orsi, Benedikt Gansen, Massimo Degano, Johannes Buchner, Roberto Sitia

{"title":"How J-chain ensures the assembly of immunoglobulin IgM pentamers.","authors":"Chiara Giannone, Xenia Mess, Ruiming He, Maria Rita Chelazzi, Annika Mayer, Anush Bakunts, Tuan Nguyen, Yevheniia Bushman, Andrea Orsi, Benedikt Gansen, Massimo Degano, Johannes Buchner, Roberto Sitia","doi":"10.1038/s44318-024-00317-9","DOIUrl":"10.1038/s44318-024-00317-9","url":null,"abstract":"Polymeric IgM immunoglobulins have high avidity for antigen and complement, and dominate primary antibody responses. They are produced either as assemblies of six µ2L2 subunits (i.e., hexamers), or as pentamers of two µ2L2 subunits and an additional protein termed J-chain (JC), which allows transcytosis across epithelia. The molecular mechanism of IgM assembly with the desired stoichiometry remained unknown. Here, we show in vitro and in cellula that JC outcompetes the sixth IgM subunit during assembly. Before insertion into IgM, JC exists as an ensemble of largely unstructured, protease-sensitive species with heterogeneous, non-native disulfide bonds. The J-chain interacts with the hydrophobic β-sheets selectively exposed by nascent pentamers. Completion of an amyloid-like core triggers JC folding and drives disulfide rearrangements that covalently stabilize JC-containing pentamers. In cells, the quality control factor ERp44 surveys IgM assembly and prevents the secretion of aberrant conformers. This mechanism allows the efficient production of high-avidity IgM for systemic or mucosal immunity.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"505-533"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781753","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

Layered entrenchment maintains essentiality in the evolution of Form I Rubisco complexes. 在形式 I Rubisco 复合物的进化过程中，层状堑壕保持了基本性。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1038/s44318-024-00311-1

Luca Schulz, Jan Zarzycki, Wieland Steinchen, Georg K A Hochberg, Tobias J Erb

{"title":"Layered entrenchment maintains essentiality in the evolution of Form I Rubisco complexes.","authors":"Luca Schulz, Jan Zarzycki, Wieland Steinchen, Georg K A Hochberg, Tobias J Erb","doi":"10.1038/s44318-024-00311-1","DOIUrl":"10.1038/s44318-024-00311-1","url":null,"abstract":"Protein complexes composed of strictly essential subunits are abundant in nature and often arise through the gradual complexification of ancestral precursor proteins. Essentiality can arise through the accumulation of changes that are tolerated in the complex state but would be deleterious for the standalone complex components. While this theoretical framework to explain how essentiality arises has been proposed long ago, it is unclear which factors cause essentiality to persist over evolutionary timescales. In this work we show that the central enzyme of photosynthesis, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), can easily start to depend on a newly recruited interaction partner through multiple, genetically distinct mechanisms that affect stability, solubility, and catalysis. We demonstrate that layering multiple mechanisms of essentiality can lead to its persistence, even if any given mechanism reverts. More broadly, our work highlights that new interaction partners can drastically re-shape which substitutions are tolerated in the proteins they are recruited into. This can lead to the evolution of multilayered essentiality through the exploration of areas of sequence space that are only accessible in the complex state.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"269-280"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669701","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

Structural insight into Okazaki fragment maturation mediated by PCNA-bound FEN1 and RNaseH2. 从结构上洞察由 PCNA 结合的 FEN1 和 RNaseH2 介导的冈崎片段成熟。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-22 DOI: 10.1038/s44318-024-00296-x

Yuhui Tian, Ningning Li, Qing Li, Ning Gao

{"title":"Structural insight into Okazaki fragment maturation mediated by PCNA-bound FEN1 and RNaseH2.","authors":"Yuhui Tian, Ningning Li, Qing Li, Ning Gao","doi":"10.1038/s44318-024-00296-x","DOIUrl":"10.1038/s44318-024-00296-x","url":null,"abstract":"PCNA is a master coordinator of many DNA-metabolic events. During DNA replication, the maturation of Okazaki fragments involves at least four DNA enzymes, all of which contain PCNA-interacting motifs. However, the temporal relationships and functional modulations between these PCNA-binding proteins are unclear. Here, we developed a strategy to purify endogenous PCNA-containing complexes from native chromatin, and characterized their structures using cryo-EM. Two structurally resolved classes (PCNA-FEN1 and PCNA-FEN1-RNaseH2 complexes) have captured a series of 3D snapshots for the primer-removal steps of Okazaki fragment maturation. These structures show that product release from FEN1 is a rate-liming step. Furthermore, both FEN1 and RNaseH2 undergo continuous conformational changes on PCNA that result in constant fluctuations in the bending angle of substrate DNA at the nick site, implying that these enzymes could regulate each other through conformational modulation of the bound DNA. The structures of the PCNA-FEN1-RNaseH2 complex confirm the toolbelt function of PCNA and suggests a potential unrecognized role of RNaseH2, as a dsDNA binding protein, in promoting the 5'-flap cleaving activity of FEN1.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"484-504"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693737","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

Intestinal NUCB2/nesfatin-1 regulates hepatic glucose production via the MC4R-cAMP-GLP-1 pathway. 肠道 NUCB2/nesfatin-1 通过 MC4R-cAMP-GLP-1 途径调节肝脏葡萄糖的产生。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-19 DOI: 10.1038/s44318-024-00300-4

Shan Geng, Shan Yang, Xuejiao Tang, Shiyao Xue, Ke Li, Dongfang Liu, Chen Chen, Zhiming Zhu, Hongting Zheng, Yuanqiang Wang, Gangyi Yang, Ling Li, Mengliu Yang

{"title":"Intestinal NUCB2/nesfatin-1 regulates hepatic glucose production via the MC4R-cAMP-GLP-1 pathway.","authors":"Shan Geng, Shan Yang, Xuejiao Tang, Shiyao Xue, Ke Li, Dongfang Liu, Chen Chen, Zhiming Zhu, Hongting Zheng, Yuanqiang Wang, Gangyi Yang, Ling Li, Mengliu Yang","doi":"10.1038/s44318-024-00300-4","DOIUrl":"10.1038/s44318-024-00300-4","url":null,"abstract":"Communication of gut hormones with the central nervous system is important to regulate systemic glucose homeostasis, but the precise underlying mechanism involved remain little understood. Nesfatin-1, encoded by nucleobindin-2 (NUCB2), a potent anorexigenic peptide hormone, was found to be released from the gastrointestinal tract, but its specific function in this context remains unclear. Herein, we found that gut nesfatin-1 can sense nutrients such as glucose and lipids and subsequently decreases hepatic glucose production. Nesfatin-1 infusion in the small intestine of NUCB2-knockout rats reduced hepatic glucose production via a gut - brain - liver circuit. Mechanistically, NUCB2/nesfatin-1 interacted directly with melanocortin 4 receptor (MC4R) through its H-F-R domain and increased cyclic adenosine monophosphate (cAMP) levels and glucagon-like peptide 1 (GLP-1) secretion in the intestinal epithelium, thus inhibiting hepatic glucose production. The intestinal nesfatin-1 -MC4R-cAMP-GLP-1 pathway and systemic gut-brain communication are required for nesfatin-1 - mediated regulation of liver energy metabolism. These findings reveal a novel mechanism of hepatic glucose production control by gut hormones through the central nervous system.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"54-74"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677405","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