Cell reports最新文献_第10页

Genome-wide mutagenesis identifies factors involved in MRSA vaginal colonization.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-13 DOI: 10.1016/j.celrep.2025.115421

Laurie M Lyon, Stephanie M Marroquin, John C Thorstenson, Luke R Joyce, Ernesto J Fuentes, Kelly S Doran, Alexander R Horswill

{"title":"Genome-wide mutagenesis identifies factors involved in MRSA vaginal colonization.","authors":"Laurie M Lyon, Stephanie M Marroquin, John C Thorstenson, Luke R Joyce, Ernesto J Fuentes, Kelly S Doran, Alexander R Horswill","doi":"10.1016/j.celrep.2025.115421","DOIUrl":"10.1016/j.celrep.2025.115421","url":null,"abstract":"Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that colonizes various body sites, including the nares, skin, and vagina. During pregnancy,colonization can lead to dysbiosis, adverse pregnancy outcomes, and invasive disease. To identify genes contributing to MRSA vaginal fitness, we performed transposon sequencing (Tn-seq) using a murine model of vaginal colonization, identifying over 250 conditionally essential genes. Five genes were validated in our murine model, including those encoding the aerobic respiration protein QoxB, bacillithiol biosynthesis component BshB2, sialic acid catabolism enzyme NanE, and staphylococcal regulator of respiration SrrAB. RNA sequencing and comparative analysis identified over 30 SrrAB-regulated genes potentially important for fitness in vaginal-like conditions, particularly under oxygen stress. These findings highlight pathways such as aerobic respiration, bacillithiol biosynthesis, sialic acid catabolism, and transcriptional regulation that support MRSA's competitive fitness in the vaginal tract.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115421"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630207","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

Phosphatase PHLPP1 is an alveolar-macrophage-intrinsic transcriptional checkpoint controlling pulmonary fibrosis. 磷酸酶 PHLPP1 是控制肺纤维化的肺泡-巨噬细胞内在转录检查点。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-12 DOI: 10.1016/j.celrep.2025.115399

Yuyu Jiang, Yunkai Zhang, Xiaohui Wang, Yan Xiang, Zeting Wang, Bo Wang, Yingying Ding, Ying Gao, Bing Rui, Jie Bai, Yue Ding, Chang Chen, Zhenzhen Zhan, Xingguang Liu

{"title":"Phosphatase PHLPP1 is an alveolar-macrophage-intrinsic transcriptional checkpoint controlling pulmonary fibrosis.","authors":"Yuyu Jiang, Yunkai Zhang, Xiaohui Wang, Yan Xiang, Zeting Wang, Bo Wang, Yingying Ding, Ying Gao, Bing Rui, Jie Bai, Yue Ding, Chang Chen, Zhenzhen Zhan, Xingguang Liu","doi":"10.1016/j.celrep.2025.115399","DOIUrl":"10.1016/j.celrep.2025.115399","url":null,"abstract":"Alveolar macrophages (AMs) are crucial for lung homeostasis, and their dysfunction causes uncontrolled fibrotic responses and pulmonary disorders. Protein phosphatases control multiple cellular events. However, whether nuclear phosphatases cooperate with histone modifiers to affect pulmonary fibrosis progress remains obscure. Here, we identified pleckstrin homology domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) as a key protective factor for pulmonary fibrosis. Transcriptomics and epigenomics data confirmed that PHLPP1 selectively targeted Kruppel-like factor 4 (KLF4) for transcriptional inhibition in AMs. Nuclear PHLPP1 directly bound and dephosphorylated histone deacetylase 8 (HDAC8) at serine 39, thereby enhancing its deacetylase enzyme activity and subsequently suppressing KLF4 expression via the decreased histone acetylation and chromatin accessibility. Thus, loss of PHLPP1 amplified KLF4-centric profibrotic transcriptional program in AMs, while intratracheal administration of Klf4-short hairpin RNA (shRNA) adeno-associated virus ameliorated lung fibrosis in PHLPP1-deficient mice. Our study implies that targeting decreased PHLPP1 in AMs might be a promising therapeutic strategy for pulmonary fibrosis.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115399"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630211","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

Uncovering the mechanism for polar sequestration of the major bacterial sugar regulator by high-throughput screens and 3D interaction modeling.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-17 DOI: 10.1016/j.celrep.2025.115436

Nitsan Albocher-Kedem, Meta Heidenreich, Amir Fadel, Elizabeta Sirotkin, Omer Goldberger, Anat Nussbaum-Shochat, Emmanuel D Levy, Ora Schueler-Furman, Maya Schuldiner, Orna Amster-Choder

{"title":"Uncovering the mechanism for polar sequestration of the major bacterial sugar regulator by high-throughput screens and 3D interaction modeling.","authors":"Nitsan Albocher-Kedem, Meta Heidenreich, Amir Fadel, Elizabeta Sirotkin, Omer Goldberger, Anat Nussbaum-Shochat, Emmanuel D Levy, Ora Schueler-Furman, Maya Schuldiner, Orna Amster-Choder","doi":"10.1016/j.celrep.2025.115436","DOIUrl":"10.1016/j.celrep.2025.115436","url":null,"abstract":"The poles of rod-shaped bacteria emerge as regulatory hubs. We have shown that enzyme I (EI), the major bacterial sugar metabolism regulator, is sequestered when not needed in TmaR phase-separated condensates in Escherichia coli cell poles. Here, we combined genetic and automated microscopy screens to identify residues in EI and TmaR that are important for their interaction and colocalization. Mutating these residues affects EI-TmaR interaction in bacteria and impairs co-phase separation in yeast. The results were used to generate an EI-TmaR interaction model, which agrees with coevolution data and is supported by conservation of the interacting residues and EI-TmaR colocalization in other species. Mutating residues predicted to interact electrostatically further supports our model. The model explains how TmaR controls EI activity and its interaction with the phosphoprotein HPr and, hence, sugar uptake. Our study highlights the importance of sugar metabolism spatial regulation during evolution and presents a way to unravel protein-protein interactions.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115436"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656287","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 basis for the reversal of human MRP4-mediated multidrug resistance by lapatinib.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-25 DOI: 10.1016/j.celrep.2025.115466

Zhipeng Xie, Jiaxiang Lv, Wei Huang, Zhikun Wu, Rongli Zhu, Zixin Deng, Feng Long

引用次数: 0

Distinct features of a peripheral T helper subset that drives the B cell response in dengue virus infection.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-11 DOI: 10.1016/j.celrep.2025.115366

Asgar Ansari, Shilpa Sachan, Jatin Ahuja, Sureshkumar Venkadesan, Bhushan Nikam, Vinod Kumar, Shweta Jain, Bhanu Pratap Singh, Poonam Coshic, Kapil Sikka, Naveet Wig, Alessandro Sette, Daniela Weiskopf, Debasisa Mohanty, Manish Soneja, Nimesh Gupta

{"title":"Distinct features of a peripheral T helper subset that drives the B cell response in dengue virus infection.","authors":"Asgar Ansari, Shilpa Sachan, Jatin Ahuja, Sureshkumar Venkadesan, Bhushan Nikam, Vinod Kumar, Shweta Jain, Bhanu Pratap Singh, Poonam Coshic, Kapil Sikka, Naveet Wig, Alessandro Sette, Daniela Weiskopf, Debasisa Mohanty, Manish Soneja, Nimesh Gupta","doi":"10.1016/j.celrep.2025.115366","DOIUrl":"10.1016/j.celrep.2025.115366","url":null,"abstract":"Dengue-virus-induced humoral immunity can increase the risk of severe disease, but the factors influencing this response are poorly understood. Here, we investigate the contribution of CD4+ T cells to B cell responses in human dengue infection. We identify a dominant peripheral PD-1+ T cell subset that accumulates in severe patients and could induce B cell differentiation via interleukin-21 (IL-21)-related pathway. Single-cell analyses reveal heterogeneity within PD-1+ cells, demonstrating the coexistence of subsets with \"helper\" (IL-21+) or \"cytotoxic\" characteristics. The IL-21+ subset displays a distinct clonotypic and transcriptomic signature compared to follicular helper T cells and persists as a memory in lymph nodes. Notably, we show that the IL-21+ subset seems to majorly drive the extrafollicular B cell responses in dengue. Our study establishes the peripheral IL-21+ subset as a potential determinant of the humoral response to dengue virus infection. These findings provide important insights into the T-cell-dependent regulation of humoral responses and can inform the design of effective dengue vaccines.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":" ","pages":"115366"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613734","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

Distinctive CD8⁺ T cell activation by antigen-presenting plasmacytoid dendritic cells compared to conventional dendritic cells.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-11 DOI: 10.1016/j.celrep.2025.115413

Renée M van der Sluis, Juan L García-Rodríguez, Ian Helstrup Nielsen, Albert Gris-Oliver, Jennifer Becker, Bibiana Costa, M Zeeshan Chaudhry, Marvin Werner, Anders Laustsen, Jesper G Pedersen, Kristine R Gammelgaard, Trine H Mogensen, Ulrich Kalinke, Luka Cicin-Sain, Rasmus O Bak, Lasse S Kristensen, Martin R Jakobsen

{"title":"Distinctive CD8+ T cell activation by antigen-presenting plasmacytoid dendritic cells compared to conventional dendritic cells.","authors":"Renée M van der Sluis, Juan L García-Rodríguez, Ian Helstrup Nielsen, Albert Gris-Oliver, Jennifer Becker, Bibiana Costa, M Zeeshan Chaudhry, Marvin Werner, Anders Laustsen, Jesper G Pedersen, Kristine R Gammelgaard, Trine H Mogensen, Ulrich Kalinke, Luka Cicin-Sain, Rasmus O Bak, Lasse S Kristensen, Martin R Jakobsen","doi":"10.1016/j.celrep.2025.115413","DOIUrl":"10.1016/j.celrep.2025.115413","url":null,"abstract":"Plasmacytoid dendritic cells (pDCs) play a pivotal role in immune responses, particularly against viral infections. pDCs exhibit diverse functions, including interferon production, cytokine secretion, and antigen presentation. Here, we investigate the antigen cross-presentation capacity of pDCs and their role in CD8+ T cell activation. Utilizing a culturing system with CD8+ T cells and autologous pDCs derived from circulating CD34+ hematopoietic stem and progenitor cells, we demonstrate that pDCs efficiently activate CD8+ T cells via cross-presentation, promoting T cell expansion and cytotoxic activity. The antigen presentation capacity of pDCs is comparable to that of monocyte-derived dendritic cells (moDCs) and myeloid dendritic cells, which are known for their efficient antigen-presentation capacity. Transcriptomic analysis reveals genetic signatures in CD8+ T cells activated by pDCs distinct from moDCs, suggesting different activation mechanisms. These findings underscore the importance of pDCs in antigen presentation and their contribution to CD8+ T cell activation.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115413"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613737","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

Downstream signaling induced by several plant Toll/interleukin-1 receptor-containing immune proteins is stable at elevated temperature.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-25 Epub Date: 2025-02-19 DOI: 10.1016/j.celrep.2025.115326

Héloïse Demont, Céline Remblière, Raphaël Culerrier, Madeline Sauvaget, Laurent Deslandes, Maud Bernoux

{"title":"Downstream signaling induced by several plant Toll/interleukin-1 receptor-containing immune proteins is stable at elevated temperature.","authors":"Héloïse Demont, Céline Remblière, Raphaël Culerrier, Madeline Sauvaget, Laurent Deslandes, Maud Bernoux","doi":"10.1016/j.celrep.2025.115326","DOIUrl":"10.1016/j.celrep.2025.115326","url":null,"abstract":"Plant immunity and, in particular, immune responses induced by nucleotide-binding leucine-rich repeat receptors (NLRs) are often dampened above the optimal plant's growth range, but the underlying molecular mechanism remains elusive. N-terminal Toll/interleukin-1 receptor (TIR) domains are self-sufficient to trigger immune signaling. We showed that the conditional activation of two well-characterized TIR-containing NLRs (TNLs) or their corresponding TIR domains alone induce the same signaling route at permissive temperature (ENHANCED DISEASE SUSCEPTIBLITY 1 [EDS1]/helper NLRs that display an RPW8-like N-terminal CCR domain [RNL] requirement and activation of the salicylic acid sector) in Arabidopsis. Yet, this signaling pathway is maintained under elevated temperatures (30°C) when induced by TIRs only but not full-length TNLs. This work underlines the need to further study how NLRs are impacted by an increase in temperature, which is particularly important to improve the resilience of plant disease resistance in a warming climate.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115326"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472329","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

The NF1 tumor suppressor regulates PD-L1 and immune evasion in melanoma.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-01 DOI: 10.1016/j.celrep.2025.115365

Diana Berry, Dan Moldoveanu, Shivshankari Rajkumar, Mathieu Lajoie, Tiffany Lin, Daméhan Tchelougou, Samridhi Sakthivel, Itai Sharon, Antoine Bernard, Sandy Pelletier, Yael Ripstein, Alan Spatz, Wilson H Miller, Rahima Jamal, Réjean Lapointe, Anne-Marie Mes-Masson, Kevin Petrecca, Ari-Nareg Meguerditchian, Keith Richardson, Beatrice Wang, May Chergui, Marie-Christine Guiot, Kevin Watters, John Stagg, T Martin Schmeing, Francis Rodier, Simon Turcotte, Catalin Mihalcioiu, Sarkis Meterissian, Ian R Watson

{"title":"The NF1 tumor suppressor regulates PD-L1 and immune evasion in melanoma.","authors":"Diana Berry, Dan Moldoveanu, Shivshankari Rajkumar, Mathieu Lajoie, Tiffany Lin, Daméhan Tchelougou, Samridhi Sakthivel, Itai Sharon, Antoine Bernard, Sandy Pelletier, Yael Ripstein, Alan Spatz, Wilson H Miller, Rahima Jamal, Réjean Lapointe, Anne-Marie Mes-Masson, Kevin Petrecca, Ari-Nareg Meguerditchian, Keith Richardson, Beatrice Wang, May Chergui, Marie-Christine Guiot, Kevin Watters, John Stagg, T Martin Schmeing, Francis Rodier, Simon Turcotte, Catalin Mihalcioiu, Sarkis Meterissian, Ian R Watson","doi":"10.1016/j.celrep.2025.115365","DOIUrl":"10.1016/j.celrep.2025.115365","url":null,"abstract":"Hotspot BRAF, hotspot NRAS, and NF1 loss-of-function mutations are found in approximately 50%, 25%, and 15% of cutaneous melanomas, respectively. Compared to mutant BRAF and NRAS, the role of NF1 loss in melanoma remains understudied. NF1 has a RAS GTPase-activating protein (GAP) function; however, studies also support NF1 RAS-independent tumor-suppressor functions. Recent reports indicate that patients with NF1 mutant melanoma have high response rates to anti-PD-1 immune checkpoint inhibitors (ICIs) for reasons that are not entirely clear. Here, we present data demonstrating that NF1 interacts with PD-L1. Furthermore, NF1 loss in melanoma lines increases PD-L1 cell surface expression through a RAS-GAP-independent mechanism. Co-culture experiments demonstrate that NF1 depletion in melanoma increases resistance to T cell killing, which can be abrogated with anti-PD-1/PD-L1 ICIs. These results support a model whereby NF1 loss leads to immune evasion through the PD-L1/PD-1 axis, providing support for the examination of anti-PD-1 therapies in other NF1 mutant cancers.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115365"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536764","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

Secreted neurofilament light chain after neuronal damage induces myeloid cell activation and neuroinflammation.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-07 DOI: 10.1016/j.celrep.2025.115382

Olga I Kahn, Sara L Dominguez, Caspar Glock, Margaret Hayne, Steve Vito, Arundhati Sengupta Ghosh, Max Adrian, Braydon L Burgess, William J Meilandt, Brad A Friedman, Casper C Hoogenraad

{"title":"Secreted neurofilament light chain after neuronal damage induces myeloid cell activation and neuroinflammation.","authors":"Olga I Kahn, Sara L Dominguez, Caspar Glock, Margaret Hayne, Steve Vito, Arundhati Sengupta Ghosh, Max Adrian, Braydon L Burgess, William J Meilandt, Brad A Friedman, Casper C Hoogenraad","doi":"10.1016/j.celrep.2025.115382","DOIUrl":"10.1016/j.celrep.2025.115382","url":null,"abstract":"Neurofilament light chain (NfL) is a neuron-specific cytoskeletal protein that provides structural support for axons and is released into the extracellular space following neuronal injury. While NfL has been extensively studied as a disease biomarker, the underlying release mechanisms and role in neurodegeneration remain poorly understood. Here, we find that neurons secrete low baseline levels of NfL, while neuronal damage triggers calpain-driven proteolysis and release of fragmented NfL. Secreted NfL activates microglial cells, which can be blocked with anti-NfL antibodies. We utilize in vivo single-cell RNA sequencing to profile brain cells after injection of recombinant NfL into the mouse hippocampus and find robust macrophage and microglial responses. Consistently, NfL knockout mice ameliorate microgliosis and delay symptom onset in the SOD1 mouse model of amyotrophic lateral sclerosis (ALS). Our results show that released NfL can activate myeloid cells in the brain and is, thus, a potential therapeutic target for neurodegenerative diseases.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115382"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582215","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

The STRIPAK complex is required for radial sorting and laminin receptor expression in Schwann cells.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-06 DOI: 10.1016/j.celrep.2025.115401

Michael R Weaver, Dominika Shkoruta, Marta Pellegatta, Caterina Berti, Marilena Palmisano, Scott Ferguson, Edward Hurley, Julianne French, Shreya Patel, Sophie Belin, Matthias Selbach, Florian Ernst Paul, Fraser Sim, Yannick Poitelon, M Laura Feltri

{"title":"The STRIPAK complex is required for radial sorting and laminin receptor expression in Schwann cells.","authors":"Michael R Weaver, Dominika Shkoruta, Marta Pellegatta, Caterina Berti, Marilena Palmisano, Scott Ferguson, Edward Hurley, Julianne French, Shreya Patel, Sophie Belin, Matthias Selbach, Florian Ernst Paul, Fraser Sim, Yannick Poitelon, M Laura Feltri","doi":"10.1016/j.celrep.2025.115401","DOIUrl":"10.1016/j.celrep.2025.115401","url":null,"abstract":"During peripheral nervous system development, Schwann cells undergo Rac1-dependent cytoskeletal reorganization as they insert cytoplasmic extensions into axon bundles to sort and myelinate individual axons. However, our understanding of the direct effectors targeted by Rac1 is limited. Here, we demonstrate that striatin-3 and MOB4 are Rac1 interactors. We show that Schwann-cell-specific ablation of striatin-3 causes defects in lamellipodia formation, and conditional Schwann cell knockout for striatins presents a severe delay in radial sorting. Finally, we demonstrate that deletion of Rac1 or striatin-1/3 in Schwann cells causes defects in the activation of Hippo pathway effectors YAP and TAZ and the expression of genes co-regulated by YAP and TAZ, such as extracellular matrix receptors. In summary, our results indicate that striatin-3 is a Rac1 interactor and that striatins are required for peripheral nervous system development and reveal a role for Rac1 in the regulation of the Hippo pathway in Schwann cells.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115401"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582218","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