Cell reports最新文献_第2页

Structural insights into prolactin-releasing peptide receptor signaling and G-protein coupling selectivity.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-02-19 DOI: 10.1016/j.celrep.2025.115337

Zhangsong Wu, Chen Qiu, Yiming Liu, Xiaoyi Yan, Qiaohui Li, Shirui Jiang, Jun Xu, Xin Pan, Fang Ye, Zhiyi Zhang, Peiruo Ning, Binghao Zhang, Lezhi Xu, Bangning Cheng, Xufu Xiang, Chungen Qian, Yang Du, Geng Chen

{"title":"Structural insights into prolactin-releasing peptide receptor signaling and G-protein coupling selectivity.","authors":"Zhangsong Wu, Chen Qiu, Yiming Liu, Xiaoyi Yan, Qiaohui Li, Shirui Jiang, Jun Xu, Xin Pan, Fang Ye, Zhiyi Zhang, Peiruo Ning, Binghao Zhang, Lezhi Xu, Bangning Cheng, Xufu Xiang, Chungen Qian, Yang Du, Geng Chen","doi":"10.1016/j.celrep.2025.115337","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115337","url":null,"abstract":"Prolactin-releasing peptide receptor (PrRPR), a notable member of the class A peptide-GPCR (G-protein-coupled receptor) family, regulates diverse physiology functions upon activation by PrRP. Herein, we reveal that PrRPR could engage with not only the Gq/11 pathway but also the Gi/o pathway. We further resolve the structures of the PrRPR-Gq and PrRPR-Gi complexes using cryoelectron microscopy (cryo-EM), with PrRP31 as the endogenous ligand. These high-resolution structures enhance our understanding of PrRPR-ligand interactions, aiding the development of targeted drugs aiming at this crucial peptide-receptor system. Comparing these structures with counterparts of other RF-amide peptide receptors accentuates the crucial function of the RF-amide motif in activating receptors and sheds light on the universal mechanism for RF-amide motif detection by RF-amide receptors. Furthermore, structural and functional analysis indicates that conformational alterations in the intracellular loops (ICLs), along with the \"wavy hook\" of Gα, may explain the selective coupling of G proteins in PrRPR signaling.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115337"},"PeriodicalIF":7.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467213","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

Overfeeding induces adipose tissue release of distinct mitochondria.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-02-18 DOI: 10.1016/j.celrep.2025.115318

Joshua H Goodman, Chloé Berland, Rajesh K Soni, Anthony W Ferrante

引用次数: 0

An Aurora kinase A-BOD1L1-PP2A B56 axis promotes chromosome segregation fidelity.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-02-18 DOI: 10.1016/j.celrep.2025.115317

Thomas J Kucharski, Irma M Vlasac, Tatiana Lyalina, Martin R Higgs, Brock C Christensen, Susanne Bechstedt, Duane A Compton

{"title":"An Aurora kinase A-BOD1L1-PP2A B56 axis promotes chromosome segregation fidelity.","authors":"Thomas J Kucharski, Irma M Vlasac, Tatiana Lyalina, Martin R Higgs, Brock C Christensen, Susanne Bechstedt, Duane A Compton","doi":"10.1016/j.celrep.2025.115317","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115317","url":null,"abstract":"Cancer cells are often aneuploid and frequently display elevated rates of chromosome mis-segregation, called chromosomal instability (CIN). CIN is caused by hyperstable kinetochore-microtubule (K-MT) attachments that reduce the correction efficiency of erroneous K-MT attachments. UMK57, a chemical agonist of the protein MCAK (mitotic centromere-associated kinesin), improves chromosome segregation fidelity in CIN cancer cells by destabilizing K-MT attachments, but cells rapidly develop resistance. To determine the mechanism, we performed unbiased screens, which revealed increased phosphorylation in cells adapted to UMK57 at Aurora kinase A phosphoacceptor sites on BOD1L1 (protein biorientation defective 1-like-1). BOD1L1 depletion or Aurora kinase A inhibition eliminated resistance to UMK57. BOD1L1 localizes to spindles/kinetochores during mitosis, interacts with the PP2A phosphatase, and regulates phosphorylation levels of kinetochore proteins, chromosome alignment, mitotic progression, and fidelity. Moreover, the BOD1L1 gene is mutated in a subset of human cancers, and BOD1L1 depletion reduces cell growth in combination with clinically relevant doses of Taxol or Aurora kinase A inhibitor.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 2","pages":"115317"},"PeriodicalIF":7.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456997","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

Structural basis of promiscuous inhibition of Listeria virulence activator PrfA by oligopeptides.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-02-17 DOI: 10.1016/j.celrep.2025.115290

Tobias Hainzl, Mariela Scortti, Cecilia Lindgren, Christin Grundström, Emilia Krypotou, José A Vázquez-Boland, A Elisabeth Sauer-Eriksson

{"title":"Structural basis of promiscuous inhibition of Listeria virulence activator PrfA by oligopeptides.","authors":"Tobias Hainzl, Mariela Scortti, Cecilia Lindgren, Christin Grundström, Emilia Krypotou, José A Vázquez-Boland, A Elisabeth Sauer-Eriksson","doi":"10.1016/j.celrep.2025.115290","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115290","url":null,"abstract":"The facultative pathogen Listeria monocytogenes uses a master regulator, PrfA, to tightly control the fitness-costly expression of its virulence factors. We found that PrfA activity is repressed via competitive occupancy of the binding site for the PrfA-activating cofactor, glutathione, by exogenous nutritional oligopeptides. The inhibitory peptides show different sequence and physicochemical properties, but how such a wide variety of oligopeptides can bind PrfA was unclear. Using crystal structure analysis of PrfA complexed with inhibitory tri- and tetrapeptides, we show here that the binding promiscuity is due to the ability of PrfA β5 in the glutathione-binding inter-domain tunnel to establish parallel or antiparallel β sheet-like interactions with the peptide backbone. Spacious tunnel pockets provide additional flexibility for unspecific peptide accommodation while providing selectivity for hydrophobic residues. Hydrophobic contributions from two adjacent peptide residues appear to be critical for efficient PrfA inhibitory binding. In contrast to glutathione, peptide binding prevents the conformational change required for the correct positioning of the DNA-binding helix-turn-helix motifs of PrfA, effectively inhibiting virulence gene expression.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 2","pages":"115290"},"PeriodicalIF":7.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457003","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

Luminescent sensing of conformational integrin activation in living cells.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-02-17 DOI: 10.1016/j.celrep.2025.115319

Giulia Villari, Noemi Gioelli, Marta Gino, Heng Zhang, Kelly Hodge, Francesca Cordero, Sara Zanivan, Jieqing Zhu, Guido Serini

{"title":"Luminescent sensing of conformational integrin activation in living cells.","authors":"Giulia Villari, Noemi Gioelli, Marta Gino, Heng Zhang, Kelly Hodge, Francesca Cordero, Sara Zanivan, Jieqing Zhu, Guido Serini","doi":"10.1016/j.celrep.2025.115319","DOIUrl":"10.1016/j.celrep.2025.115319","url":null,"abstract":"Integrins are major receptors for secreted extracellular matrix, playing crucial roles in physiological and pathological contexts, such as angiogenesis and cancer. Regulation of the transition between inactive and active conformation is key for integrins to fulfill their functions, and pharmacological control of those dynamics may have therapeutic applications. We create and validate a prototypic luminescent β1 integrin activation sensor (β1IAS) by introducing a split luciferase into an activation reporting site between the βI and the hybrid domains. As a recombinant protein in both solution and living cells, β1IAS accurately reports β1 integrin activation in response to (bio)chemical and physical stimuli. A short interfering RNA (siRNA) high-throughput screening on live β1IAS knockin endothelial cells unveils hitherto unknown regulators of β1 integrin activation, such as β1 integrin inhibitors E3 ligase Pja2 and vascular endothelial growth factor B (VEGF-B). This split-luciferase-based strategy provides an in situ label-free measurement of integrin activation and may be applicable to other β integrins and receptors.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 2","pages":"115319"},"PeriodicalIF":7.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448333","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

Identification of CCL3 as a Schwann cell chemotactic factor essential for nerve regeneration.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-02-16 DOI: 10.1016/j.celrep.2025.115322

Lucie Van Emmenis, Guillem Mòdol-Caballero, Elizabeth Harford-Wright, Alex Power, Anne-Laure Cattin, Ian J White, Giulia Casal, Inês Boal-Carvalho, Clare L Bennett, Alison C Lloyd

{"title":"Identification of CCL3 as a Schwann cell chemotactic factor essential for nerve regeneration.","authors":"Lucie Van Emmenis, Guillem Mòdol-Caballero, Elizabeth Harford-Wright, Alex Power, Anne-Laure Cattin, Ian J White, Giulia Casal, Inês Boal-Carvalho, Clare L Bennett, Alison C Lloyd","doi":"10.1016/j.celrep.2025.115322","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115322","url":null,"abstract":"Peripheral nerves regenerate following injury, in contrast to those of the central nervous system. This involves the collective migration of Schwann cell (SC) cords, which transport regrowing axons across the wound site. The SC cords migrate along a newly formed vasculature, which bridges the wound site in response to vascular endothelial growth factor, secreted by hypoxic macrophages. However, the directional signals by which SC cords navigate the long distances across the wound, in the absence of those that guide axons during development, remain unknown. Here, we identify CCL3 as the SC chemotactic factor, secreted by hypoxic macrophages, responsible for this process. We show that CCL3 promotes collective SC migration and axonal regrowth in vivo and, using genetic mouse models and widely used CCL3 inhibitors, that CCL3 is essential for effective nerve regeneration. These findings have therapeutic implications for both promoting nerve repair and inhibiting the aberrant nerve growth associated with trauma and disease.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 2","pages":"115322"},"PeriodicalIF":7.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439994","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

Hybrid immunity-based induction of durable pan-endemic-coronavirus immunity in the elderly.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-02-16 DOI: 10.1016/j.celrep.2025.115314

Lucie Loyal, Julian Braun, Ulf Reimer, Lil Meyer-Arndt, Larissa Henze, Beate Kruse, Manuela Dingeldey, Maike Mangold, Janina Behrens, Pinkus Tober Lau, Janine Michel, Marica Grossegesse, Karsten Schnatbaum, Holger Wenschuh, Wibke Johannis, Veronica Di Cristanziano, Andreas Nitsche, Florian Klein, Leif-Erik Sander, Andreas Thiel

{"title":"Hybrid immunity-based induction of durable pan-endemic-coronavirus immunity in the elderly.","authors":"Lucie Loyal, Julian Braun, Ulf Reimer, Lil Meyer-Arndt, Larissa Henze, Beate Kruse, Manuela Dingeldey, Maike Mangold, Janina Behrens, Pinkus Tober Lau, Janine Michel, Marica Grossegesse, Karsten Schnatbaum, Holger Wenschuh, Wibke Johannis, Veronica Di Cristanziano, Andreas Nitsche, Florian Klein, Leif-Erik Sander, Andreas Thiel","doi":"10.1016/j.celrep.2025.115314","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115314","url":null,"abstract":"Repeated vaccinations and infections have led to diverse states of hybrid immunity against SARS-CoV-2 in the global population. However, age and comorbidities can compromise protection against severe disease, and antibody-mediated immunity is undercut by viral immune escape mutations. Whether and to what extent durable T cell responses compensate for reduced humoral immunity, particularly in the elderly, have not been investigated. Here, we utilize SARS-CoV-2-specific and pan-coronavirus-derived peptide pools, including or excluding spike glycoprotein-derived epitopes, to measure vaccination and infection induced pan-human endemic coronavirus (PHEC)-directed T cell immunity. In contrast to vaccinated individuals, hybrid immunity induced by vaccination and SARS-CoV-2 infection comprises high frequencies of PHEC-reactive T cells with comparable frequencies and functional TCR avidities across all age groups. With waning humoral immunity and vulnerability to escape mutations, PHEC-reactive T cells may provide critical protection. Our findings underscore the importance of incorporating pan-coronavirus T cell epitopes in future vaccine strategies.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 2","pages":"115314"},"PeriodicalIF":7.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439992","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

Non-ionotropic signaling through the NMDA receptor GluN2B carboxy-terminal domain drives dendritic spine plasticity and reverses fragile X phenotypes.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-02-16 DOI: 10.1016/j.celrep.2025.115311

Stephanie A Barnes, Aurore Thomazeau, Peter S B Finnie, Maxwell J Heinrich, Arnold J Heynen, Noburu H Komiyama, Seth G N Grant, Frank S Menniti, Emily K Osterweil, Mark F Bear

{"title":"Non-ionotropic signaling through the NMDA receptor GluN2B carboxy-terminal domain drives dendritic spine plasticity and reverses fragile X phenotypes.","authors":"Stephanie A Barnes, Aurore Thomazeau, Peter S B Finnie, Maxwell J Heinrich, Arnold J Heynen, Noburu H Komiyama, Seth G N Grant, Frank S Menniti, Emily K Osterweil, Mark F Bear","doi":"10.1016/j.celrep.2025.115311","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115311","url":null,"abstract":"N-methyl-D-aspartate (NMDA)-induced spine shrinkage proceeds independently of ion flux and requires the initiation of de novo protein synthesis. Using subtype-selective pharmacological and genetic tools, we find that structural plasticity is dependent on ligand binding to GluN2B-containing NMDA receptors (NMDARs) and signaling via the GluN2B carboxy-terminal domain (CTD). Disruption of non-ionotropic signaling by replacing the GluN2B CTD with the GluN2A CTD leads to an increase in spine density, dysregulated basal protein synthesis, exaggerated long-term depression mediated by G-protein-coupled metabotropic glutamate receptors (mGluR-LTD), and epileptiform activity reminiscent of phenotypes observed in the Fmr1 knockout (KO) model of fragile X syndrome. By crossing the Fmr1 KO mice with animals in which the GluN2A CTD has been replaced with the GluN2B CTD, we observe a correction of these core fragile X phenotypes. These findings suggest that non-ionotropic NMDAR signaling through GluN2B may represent a novel therapeutic target for the treatment of fragile X and related causes of intellectual disability and autism.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":" ","pages":"115311"},"PeriodicalIF":7.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472313","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

Competition propels, rather than limits, the success of low-affinity B cells in the germinal center response.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-02-15 DOI: 10.1016/j.celrep.2025.115334

Runhan Li, Keyan Bao, Can Liu, Xuejing Ma, Zhaolin Hua, Ping Zhu, Baidong Hou

{"title":"Competition propels, rather than limits, the success of low-affinity B cells in the germinal center response.","authors":"Runhan Li, Keyan Bao, Can Liu, Xuejing Ma, Zhaolin Hua, Ping Zhu, Baidong Hou","doi":"10.1016/j.celrep.2025.115334","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115334","url":null,"abstract":"The germinal center (GC) sets an environment where antigen-specific B cells are compelled to continuously increase their affinity to compete for the antigen and obtain Tfh help for survival and propagation. Previous studies indicated that low-affinity B cells are disadvantaged in the presence of high-affinity ones, suggesting that competition may lead to the elimination of low-affinity B cells and their descendants. However, using a multivalent virus-mimicking antigen, our study demonstrates that low-affinity B cells not only successfully participate in GC responses alongside high-affinity B cells but also undergo accelerated affinity maturation under the more stringent competition. Furthermore, our cryo-electron-microscopy-based structural analysis reveals that both low-affinity and high-affinity B cells compete for the same antigenic epitope. Although the applicability of this idealized GC competition to true pathogen-induced responses remains uncertain, this change in perspective on the role of competition in low-affinity B cell evolution provides valuable insights for vaccine development.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 2","pages":"115334"},"PeriodicalIF":7.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432595","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

Dendritic cell phagosomes recruit GRASP55 for export of antigen-loaded MHC molecules.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-02-15 DOI: 10.1016/j.celrep.2025.115333

Ignacio Cebrian, Sofía Dinamarca, María Jesús Pena Rodríguez, Elena Priego, Nathalie Brouwers, Martina Barends, Jamina Brunnberg, Robert Tampé, Nicolas Blanchard, David Sancho, Vivek Malhotra

{"title":"Dendritic cell phagosomes recruit GRASP55 for export of antigen-loaded MHC molecules.","authors":"Ignacio Cebrian, Sofía Dinamarca, María Jesús Pena Rodríguez, Elena Priego, Nathalie Brouwers, Martina Barends, Jamina Brunnberg, Robert Tampé, Nicolas Blanchard, David Sancho, Vivek Malhotra","doi":"10.1016/j.celrep.2025.115333","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115333","url":null,"abstract":"Dendritic cells (DCs) present exogenous antigens via major histocompatibility complex class I (MHC-I) and MHC class II (MHC-II) molecules, activating CD8+ and CD4+ T cells. A critical but poorly understood step in this process is the trafficking of peptide-loaded MHC molecules from the endocytic system to the cell surface. In this study, we demonstrate that the Golgi reassembly-stacking protein of 55 kDa (GRASP55), which has been shown to have no role in stacking, is essential for antigen presentation. Using soluble, bead-coated, and bacterial-bound antigens, we found significantly impaired exogenous antigen presentation in GRASP55-deficient bone-marrow-derived DCs (BMDCs). Notably, GRASP55 was recruited to late phagosomes, and our data suggest that it is crucial for sorting MHC-I and MHC-II molecules, facilitating their trafficking to the plasma membrane. Our findings highlight the vital role of GRASP55 in the intracellular transport of MHC molecules bound to their respective peptides during exogenous antigen presentation.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 2","pages":"115333"},"PeriodicalIF":7.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432597","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