Cell Research最新文献_第8页

Self-RNA Rmrp pre-dimerizes TLR3 for immune activation 自rna Rmrp使TLR3预二聚体参与免疫激活。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-29 DOI: 10.1038/s41422-025-01184-7

Ailin Han, Richard A. Flavell

引用次数: 0

Targeting NNMT in fibroblasts reawakens T cells and restores antitumor immunity 靶向成纤维细胞中的NNMT可唤醒T细胞并恢复抗肿瘤免疫。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-24 DOI: 10.1038/s41422-025-01181-w

Moumita Sarkar, Yi Jiang, Raghu Kalluri

引用次数: 0

ATP-dependent one-dimensional movement maintains immune homeostasis by suppressing spontaneous MDA5 filament assembly atp依赖的一维运动通过抑制自发的MDA5丝组装来维持免疫稳态。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-19 DOI: 10.1038/s41422-025-01183-8

Xiao-Peng Han, Ming Rao, Yu Chang, Jun-Yan Zhu, Jun Cheng, Yu-Ting Li, Wu Qiong, Si-Chao Ye, Qiurong Zhang, Shao-Qing Zhang, Ling-Ling Chen, Fajian Hou, Jin Zhong, Jiaquan Liu

{"title":"ATP-dependent one-dimensional movement maintains immune homeostasis by suppressing spontaneous MDA5 filament assembly","authors":"Xiao-Peng Han, Ming Rao, Yu Chang, Jun-Yan Zhu, Jun Cheng, Yu-Ting Li, Wu Qiong, Si-Chao Ye, Qiurong Zhang, Shao-Qing Zhang, Ling-Ling Chen, Fajian Hou, Jin Zhong, Jiaquan Liu","doi":"10.1038/s41422-025-01183-8","DOIUrl":"10.1038/s41422-025-01183-8","url":null,"abstract":"MDA5 is a RIG-I-like receptor (RLR) that recognizes viral double-stranded RNA (dsRNA) to initiate the innate immune response. Its activation requires filament formation along the dsRNA, which triggers the oligomerization of N-terminal caspase activation and recruitment domains. The ATPase activity of MDA5 is critical for immune homeostasis, likely by regulating filament assembly. However, the molecular basis underlying this process remains poorly understood. Here, we show that MDA5 operates as an ATP-hydrolysis-driven motor that translocates along dsRNA in a one-dimensional (1D) manner. Multiple MDA5 motors can cooperatively load onto a single dsRNA, but their movements rarely synchronize, inhibiting spontaneous filament formation and activation. LGP2, a key regulator of MDA5 signaling, recognizes MDA5 motors and blocks their movement, thereby promoting filament assembly through a translocation-directed mechanism. This unique assembly strategy underscores the role of 1D motion in higher-order protein oligomerization and reveals a novel mechanism for maintaining immune homeostasis.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 11","pages":"900-912"},"PeriodicalIF":25.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01183-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089897","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

White matter interactome in vascular dementia 血管性痴呆的白质相互作用。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-17 DOI: 10.1038/s41422-025-01175-8

Stefan Wendt, Brian A. MacVicar

引用次数: 0

Deconstructing the architecture of memory engrams 解构记忆印迹的架构。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-17 DOI: 10.1038/s41422-025-01179-4

Yi Zhong, Bo Lei

引用次数: 0

Soluble tissue factor generated by necroptosis-triggered shedding is responsible for thrombosis 坏死引发的脱落所产生的可溶性组织因子是导致血栓形成的原因

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-12 DOI: 10.1038/s41422-025-01167-8

Peixing Wan, Swati Choksi, Yeon-Ji Park, Xin Chen, Jiong Yan, Sahar Foroutannejad, Zhaoshan Liu, Jichun Chen, Ross Lake, Chengyu Liu, Zheng-Gang Liu

{"title":"Soluble tissue factor generated by necroptosis-triggered shedding is responsible for thrombosis","authors":"Peixing Wan, Swati Choksi, Yeon-Ji Park, Xin Chen, Jiong Yan, Sahar Foroutannejad, Zhaoshan Liu, Jichun Chen, Ross Lake, Chengyu Liu, Zheng-Gang Liu","doi":"10.1038/s41422-025-01167-8","DOIUrl":"10.1038/s41422-025-01167-8","url":null,"abstract":"Tissue factor (TF) is a cell surface protein critical for normal hemostasis and pathological thrombosis. Necroptosis is a form of regulated necrosis associated with different diseases. Here, we reported the identification of the first functional soluble tissue factor (sTF) in mediating blood coagulation, shed from the membrane full-length TF (flTF) by proteases, ADAMs, during necroptosis. By generating sTF-specific antibody and transgenic mice carrying knockin mutations at the ADAM cleavage site of TF (T211V212 mutated to E211E212), we demonstrated that this sTF is responsible for necroptosis-related thrombosis in inflammation and viral infection mouse models. Importantly, we showed that eliminating necroptosis or the cleavage of the flTF blocked the production of sTF and prevented thrombosis in mice. We also detected sTF in the plasma of human COVID-19 patients and showed that SARS-CoV-2 pseudovirus induced sTF production. Our findings demonstrated that the sTF plays a major role in thrombosis under necroptosis-related pathological conditions and provided a diagnostic marker and potential therapies for treating thrombosis without affecting hemostasis.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 11","pages":"840-858"},"PeriodicalIF":25.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01167-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035310","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

An anti-inflammatory autophagic target in chronic diseases 慢性疾病中的抗炎自噬靶点

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-11 DOI: 10.1038/s41422-025-01176-7

Prithvi Reddy Akepati, Vojo Deretic

引用次数: 0

APOL proteins tune gut immunity via commensal lipid recognition APOL蛋白通过共生脂质识别调节肠道免疫

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-08 DOI: 10.1038/s41422-025-01166-9

Shohei Asami, Hiroshi Ohno

引用次数: 0

Molecular characterization of endosomal self RNA Rmrp-engaged TLR3 dimerization to prime innate activation 内体自身RNA rmrp参与TLR3二聚化以启动先天激活的分子特征。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-08 DOI: 10.1038/s41422-025-01178-5

Shikun Zhang, Bo Li, Lun Liu, Dongsheng Gong, Deyu Zhang, Fengjiang Liu, Xiuna Yang, Hua Qin, Deling Kong, Shuyang Zhang, Zihe Rao, Xuetao Cao

{"title":"Molecular characterization of endosomal self RNA Rmrp-engaged TLR3 dimerization to prime innate activation","authors":"Shikun Zhang, Bo Li, Lun Liu, Dongsheng Gong, Deyu Zhang, Fengjiang Liu, Xiuna Yang, Hua Qin, Deling Kong, Shuyang Zhang, Zihe Rao, Xuetao Cao","doi":"10.1038/s41422-025-01178-5","DOIUrl":"10.1038/s41422-025-01178-5","url":null,"abstract":"The pre-dimerization of endosome-localized RNA sensor Toll-like receptor 3 (TLR3) is required for its innate recognition, yet how TLR3 pre-dimers are formed and precisely primed for innate activation remains unclear. Here, we demonstrate that endosome-localized self RNA Rmrp directly binds to TLR3 and induces TLR3 dimerization in the early endosome but does not interact with endosome-localized TLR7, TLR8, TLR9 or cytoplasmic RNA sensor RIG-I under homeostatic conditions. Cryo-EM structure of Rmrp–TLR3 complex reveals a novel lapped conformation of TLR3 dimer engaged by Rmrp, which is distinct from the activation mechanism by dsRNA and the specific structural feature at the 3’-end of Rmrp is critical for its functional interaction with TLR3. Furthermore, K42 residue of TLR3 is essential for binding to Rmrp and subsequent dimerization. Rmrp dissociates from TLR3 following endosomal acidification, generating a matured TLR3 dimer which is primed for innate recognition and activation. Myeloid-cell deficiency of Rmrp reduces TLR3 dimerization and attenuates TLR3-mediated antiviral responses against influenza A both in vitro and in vivo. These findings elucidate the structural mode of self RNA Rmrp-primed TLR3 dimerization and ready for efficient innate recognition on endosomal membrane, extending our knowledge of how membrane-associated TLRs pre-dimerize and suggesting a new function of subcellular localized self RNAs in empowering innate activation.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 11","pages":"824-839"},"PeriodicalIF":25.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008738","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

Osteocalcin has many tricks to get γ-carboxylated 骨钙素有很多方法来使γ-羧化

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-05 DOI: 10.1038/s41422-025-01177-6

Mathieu Ferron

引用次数: 0