Cell reports最新文献_第6页

Structural basis of oligomerization-modulated activation and autoinhibition of orphan receptor GPR3.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-28 DOI: 10.1016/j.celrep.2025.115478

Hao Chang, Xiaoting Li, Hongqing Tu, Lijie Wu, Yanan Yu, Junlin Liu, Na Chen, Wei L Shen, Tian Hua

引用次数: 0

PDZD8 promotes autophagy at ER-lysosome membrane contact sites to regulate activity-dependent synaptic growth.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-28 DOI: 10.1016/j.celrep.2025.115483

Rajan S Thakur, Kate M O'Connor-Giles

引用次数: 0

SWI/SNF complex-mediated ZNF410 cooperative binding maintains chromatin accessibility and enhancer activity.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-28 DOI: 10.1016/j.celrep.2025.115476

Siyuan Xu, Chuxuan Peng, Ren Ren, Haowen Lu, Han Zhao, Sijian Xia, Yijie Shen, Bin Xu, Haoyue Zhang, Xiaodong Cheng, Gerd A Blobel, Xianjiang Lan

{"title":"SWI/SNF complex-mediated ZNF410 cooperative binding maintains chromatin accessibility and enhancer activity.","authors":"Siyuan Xu, Chuxuan Peng, Ren Ren, Haowen Lu, Han Zhao, Sijian Xia, Yijie Shen, Bin Xu, Haoyue Zhang, Xiaodong Cheng, Gerd A Blobel, Xianjiang Lan","doi":"10.1016/j.celrep.2025.115476","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115476","url":null,"abstract":"The clustering of multiple transcription factor binding sites (TFBSs) for the same TF has proved to be a pervasive feature of cis-regulatory elements in the eukaryotic genome. However, the contribution of binding sites within the homotypic clusters of TFBSs (HCTs) to TF binding and target gene expression remains to be understood. Here, we characterize the CHD4 enhancers that harbor unique functional ZNF410 HCTs genome wide. We uncover that ZNF410 controls chromatin accessibility and activity of the CHD4 enhancer regions. We demonstrate that ZNF410 binds to the HCTs in a collaborative fashion, further conferring transcriptional activation. In particular, three ZNF410 motifs (sub-HCTs) located at 3' end of the distal enhancer act as \"switch motifs\" to control chromatin accessibility and enhancer activity. Mechanistically, the SWI/SNF complex is selectively required to mediate cooperative ZNF410 binding for CHD4 expression. Together, our findings expose a complex functional hierarchy of homotypic clustered motifs, which cooperate to fine-tune target gene expression.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115476"},"PeriodicalIF":7.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751281","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 HAVCR1-centric host factor network drives Zika virus vertical transmission.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-28 DOI: 10.1016/j.celrep.2025.115464

Wenzhe Yu, Jun Tao, Hongmin Cao, Wanshan Zheng, Beiang Zhang, Yue Zhang, Peiqun Xu, Yiwei Zhang, Xuan Liu, Yinan Wang, Han Cai, Gang Liu, Fan Liu, Haibin Wang, Haiyan Zhao, Indira U Mysorekar, Xiaoqian Hu, Bin Cao

{"title":"The HAVCR1-centric host factor network drives Zika virus vertical transmission.","authors":"Wenzhe Yu, Jun Tao, Hongmin Cao, Wanshan Zheng, Beiang Zhang, Yue Zhang, Peiqun Xu, Yiwei Zhang, Xuan Liu, Yinan Wang, Han Cai, Gang Liu, Fan Liu, Haibin Wang, Haiyan Zhao, Indira U Mysorekar, Xiaoqian Hu, Bin Cao","doi":"10.1016/j.celrep.2025.115464","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115464","url":null,"abstract":"Zika virus (ZIKV) vertical transmission results in devastating congenital malformations and pregnancy complications; however, the specific receptor and host factors facilitating ZIKV maternal-fetal transmission remain elusive. Here, we employ a genome-wide CRISPR screening and identify multiple placenta-intrinsic factors modulating ZIKV infection. Our study unveils that hepatitis A virus cellular receptor 1 (HAVCR1) serves as a primary receptor governing ZIKV entry in placental trophoblasts. The GATA3-HAVCR1 axis regulates heterogeneous cell tropism in the placenta. Notably, placenta-specific Havcr1 deletion in mice significantly impairs ZIKV transplacental transmission and associated adverse pregnancy outcomes. Mechanistically, the immunoglobulin variable-like domain of HAVCR1 binds to ZIKV via domain III of envelope protein and virion-associated phosphatidylserine. Proteomic profiling and function analyses reveal that AP2S1 cooperates with HAVCR1 for ZIKV internalization through clathrin-mediated endocytosis. Overall, our work underscores the pivotal role of HAVCR1 in mediating ZIKV vertical transmission and highlights a therapeutic target for alleviating congenital Zika syndrome.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115464"},"PeriodicalIF":7.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742377","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

Molecular parameters governing antibody FcγR signaling and effector functions in the context of HIV envelope.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-28 DOI: 10.1016/j.celrep.2025.115331

Michael V Bick, Eduard Puig, David Beauparlant, Rebecca Nedellec, Iszac Burton, Keihvan Ardaghi, Thea R Zalunardo, Raiza Bastidas, Xuduo Li, Javier Guenaga, Wen-Hsin Lee, Richard Wyatt, Wenwen Zhu, Max Crispin, Gabriel Ozorowski, Andrew B Ward, Dennis R Burton, Lars Hangartner

{"title":"Molecular parameters governing antibody FcγR signaling and effector functions in the context of HIV envelope.","authors":"Michael V Bick, Eduard Puig, David Beauparlant, Rebecca Nedellec, Iszac Burton, Keihvan Ardaghi, Thea R Zalunardo, Raiza Bastidas, Xuduo Li, Javier Guenaga, Wen-Hsin Lee, Richard Wyatt, Wenwen Zhu, Max Crispin, Gabriel Ozorowski, Andrew B Ward, Dennis R Burton, Lars Hangartner","doi":"10.1016/j.celrep.2025.115331","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115331","url":null,"abstract":"Antibody effector functions contribute to the immune response to pathogens and can influence the efficacy of antibodies as therapeutics. To date, however, there is limited information on the molecular parameters that govern fragment crystallizable (Fc) effector functions. In this study, using AI-assisted protein design, the influences of binding kinetics, epitope location, and stoichiometry of binding on cellular Fc effector functions were investigated using engineered HIV-1 envelope as a model antigen. For this antigen, stoichiometry of binding was found to be the primary molecular determinant of FcγRIIIa signaling, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis, while epitope location and antibodybinding kinetics, at least in the ranges investigated, were of no substantial impact. These findings are of importance for informing the development of vaccination strategies against HIV-1 and, possibly, other viral pathogens.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115331"},"PeriodicalIF":7.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751161","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

Septo-hypothalamic regulation of binge-like alcohol consumption by the nociceptin system.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-27 DOI: 10.1016/j.celrep.2025.115482

Harold Haun, Raul Hernandez, Luzi Yan, Meghan Flanigan, Olivia Hon, Sophia Lee, Hernán Méndez, Alison Roland, Lisa Taxier, Thomas Kash

{"title":"Septo-hypothalamic regulation of binge-like alcohol consumption by the nociceptin system.","authors":"Harold Haun, Raul Hernandez, Luzi Yan, Meghan Flanigan, Olivia Hon, Sophia Lee, Hernán Méndez, Alison Roland, Lisa Taxier, Thomas Kash","doi":"10.1016/j.celrep.2025.115482","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115482","url":null,"abstract":"High-intensity alcohol drinking during binge episodes contributes to the socioeconomic burden created by alcohol use disorders (AUDs), and nociceptin receptor (NOP) antagonists have emerged as a promising intervention. To better understand the contribution of the NOP system to binge drinking, we found that nociceptin-containing neurons of the lateral septum (LSPnoc) displayed increased excitability during withdrawal from binge-like alcohol drinking. LSPnoc activation promoted active avoidance and potentiated binge-like drinking behavior, whereas silencing of this population reduced alcohol drinking. LSPnoc form robust monosynaptic inputs locally within the LS and genetic deletion of NOP or microinjection of a NOP antagonist into the LS decreased alcohol intake. LSPnoc also project to the lateral hypothalamus and supramammillary nucleus of the hypothalamus, and genetic deletion of NOP from each site reduced alcohol drinking. Together, these findings implicate the septo-hypothalamic nociceptin system in excessive alcohol consumption and support NOP antagonist development for the treatment of AUD.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115482"},"PeriodicalIF":7.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735650","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

Bilirubin metabolism in the liver orchestrates antiviral innate immunity in the body.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-27 DOI: 10.1016/j.celrep.2025.115481

Qian Du, Wei He, Xiangjie Chen, Jin Liu, Mingcheng Guan, Yichang Chen, Meixia Chen, Yukang Yuan, Yibo Zuo, Ying Miao, Qin Wang, Haiyan Zhou, Yanli Liu, Jingting Jiang, Hui Zheng

{"title":"Bilirubin metabolism in the liver orchestrates antiviral innate immunity in the body.","authors":"Qian Du, Wei He, Xiangjie Chen, Jin Liu, Mingcheng Guan, Yichang Chen, Meixia Chen, Yukang Yuan, Yibo Zuo, Ying Miao, Qin Wang, Haiyan Zhou, Yanli Liu, Jingting Jiang, Hui Zheng","doi":"10.1016/j.celrep.2025.115481","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115481","url":null,"abstract":"Bilirubin metabolism crucially maintains normal liver function, but whether it contributes to antiviral immunity remains unknown. Here, we reveal that the liver bilirubin metabolic pathway facilitates antiviral innate immunity of the body. We discovered that viral infection upregulates uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) expression in the liver, which in turn stabilizes IRF3 proteins to promote type I interferon (IFN-I) production. Moreover, we found that serum unconjugated bilirubin (UCB), a unique physiological substrate of UGT1A1, can competitively inhibit the binding of IFN-I to IFN-I receptor 2 (IFNAR2), thus attenuating IFN-I-induced antiviral signaling of the body. Accordingly, effective bilirubin metabolism in the liver promotes antiviral immunity of the body by specifically employing liver UGT1A1-mediated enhancement of IFN-I production and reducing serum bilirubin-mediated inhibition of IFN-I signaling. This study uncovers the significance of bilirubin metabolism in antiviral innate immunity and demonstrates that conventional IFN-I therapy is less efficient for patients with hepatitis B virus (HBV) with high levels of bilirubin.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115481"},"PeriodicalIF":7.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735595","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

Orchestration of pluripotent stem cell genome reactivation during mitotic exit.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-27 DOI: 10.1016/j.celrep.2025.115486

Silja Placzek, Ludovica Vanzan, Cédric Deluz, David M Suter

引用次数: 0

The impact of Coronavirus Nsp1 on host mRNA degradation is independent of its role in translation inhibition.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-27 DOI: 10.1016/j.celrep.2025.115488

Emilie Bäumlin, Dominic Andenmatten, Jonas Luginbühl, Aurélien Lalou, Nino Schwaller, Evangelos D Karousis

{"title":"The impact of Coronavirus Nsp1 on host mRNA degradation is independent of its role in translation inhibition.","authors":"Emilie Bäumlin, Dominic Andenmatten, Jonas Luginbühl, Aurélien Lalou, Nino Schwaller, Evangelos D Karousis","doi":"10.1016/j.celrep.2025.115488","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115488","url":null,"abstract":"When host cells are infected with coronaviruses, the first viral protein produced is non-structural protein 1 (Nsp1). This protein inhibits host protein synthesis and induces host mRNA degradation to enhance viral proliferation. Despite its critical role, the mechanism by which Nsp1 mediates cellular mRNA degradation remains unclear. In this study, we use cell-free translation to address how host mRNA stability is regulated by Nsp1. We reveal that SARS-CoV-2 Nsp1 binding to the ribosome is enough to trigger mRNA degradation independently of ribosome collisions or active translation. MERS-CoV Nsp1 inhibits translation without triggering degradation, highlighting mechanistic differences between the two Nsp1 counterparts. Nsp1 and viral mRNAs appear to co-evolve, rendering viral mRNAs immune to Nsp1-mediated degradation in SARS-CoV-2, MERS-CoV, and Bat-Hp viruses. By providing insights into the mode of action of Nsp1, our study helps to understand the biology of Nsp1 better and find strategies for therapeutic targeting against coronaviral infections.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115488"},"PeriodicalIF":7.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735653","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

Neural correlates of visual object recognition in rats.

IF 7.5 1区生物学

Cell reports Pub Date : 2025-03-26 DOI: 10.1016/j.celrep.2025.115461

Juliana Y Rhee, César Echavarría, Edward Soucy, Joel Greenwood, Javier A Masís, David D Cox

引用次数: 0