Cell Research最新文献

KCNQ1 and PIP2: it takes two to tango. KCNQ1和PIP2：一个巴掌拍不响。

IF 44.1 1区生物学

Cell Research Pub Date : 2025-10-23 DOI: 10.1038/s41422-025-01189-2

Alicia De La Cruz,H Peter Larsson

引用次数: 0

Intestinal GAPs: neuro-epithelial-immune modules for liver protection. 肠间隙：用于肝脏保护的神经上皮免疫模块。

IF 44.1 1区生物学

Cell Research Pub Date : 2025-10-16 DOI: 10.1038/s41422-025-01188-3

Manuel O Jakob,Andreas Diefenbach

引用次数: 0

LGP2 stops MDA5 translocation to start antiviral signaling. LGP2阻止MDA5易位启动抗病毒信号传导。

IF 44.1 1区生物学

Cell Research Pub Date : 2025-10-15 DOI: 10.1038/s41422-025-01187-4

Jiyoung Jang,Myung Hyun Jo

引用次数: 0

Trained immunity: induction of an inflammatory memory in disease. 训练免疫：疾病中炎症记忆的诱导。

IF 44.1 1区生物学

Cell Research Pub Date : 2025-10-14 DOI: 10.1038/s41422-025-01171-y

Titus Schlüter,Yuri van Elsas,Bram Priem,Athanasios Ziogas,Mihai G Netea

引用次数: 0

Secondary structure transitions and dual PIP2 binding define cardiac KCNQ1-KCNE1 channel gating. 二级结构转变和双PIP2结合定义心脏KCNQ1-KCNE1通道门控。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-10-02 DOI: 10.1038/s41422-025-01182-9

Ling Zhong, Xiaoqing Lin, Xinyu Cheng, Shuangyan Wan, Yaoguang Hua, Weiwei Nan, Bin Hu, Xiangjun Peng, Zihan Zhou, Qiansen Zhang, Huaiyu Yang, Frank Noé, Zhenzhen Yan, Dexiang Jiang, Hangyu Zhang, Fengjiao Liu, Chenxin Xiao, Zhuo Zhou, Yimin Mou, Haijie Yu, Lijuan Ma, Chen Huang, Vincent Kam Wai Wong, Sookja Kim Chung, Bing Shen, Zhi-Hong Jiang, Erwin Neher, Wandi Zhu, Jin Zhang, Panpan Hou

{"title":"Secondary structure transitions and dual PIP2 binding define cardiac KCNQ1-KCNE1 channel gating.","authors":"Ling Zhong, Xiaoqing Lin, Xinyu Cheng, Shuangyan Wan, Yaoguang Hua, Weiwei Nan, Bin Hu, Xiangjun Peng, Zihan Zhou, Qiansen Zhang, Huaiyu Yang, Frank Noé, Zhenzhen Yan, Dexiang Jiang, Hangyu Zhang, Fengjiao Liu, Chenxin Xiao, Zhuo Zhou, Yimin Mou, Haijie Yu, Lijuan Ma, Chen Huang, Vincent Kam Wai Wong, Sookja Kim Chung, Bing Shen, Zhi-Hong Jiang, Erwin Neher, Wandi Zhu, Jin Zhang, Panpan Hou","doi":"10.1038/s41422-025-01182-9","DOIUrl":"https://doi.org/10.1038/s41422-025-01182-9","url":null,"abstract":"The KCNQ1 + KCNE1 potassium channel complex produces the slow delayed rectifier current (IKs) critical for cardiac repolarization. Loss-of-function mutations in KCNQ1 and KCNE1 cause long QT syndrome (LQTS) types 1 and 5 (LQT1/LQT5), accounting for over one-third of clinical LQTS cases. Despite prior structural work on KCNQ1 and KCNQ1 + KCNE3, the structural basis of KCNQ1 + KCNE1 remains unresolved. Using cryo-electron microscopy and electrophysiology, we determined high-resolution (2.5-3.4 Å) structures of human KCNQ1APO, and KCNQ1 + KCNE1 in both closed and open states. KCNE1 occupies a pivotal position at the interface of three KCNQ1 subunits, inducing six helix-to-loop transitions in KCNQ1 transmembrane segments. Three of them occur at both ends of the S4-S5 linker, maintaining a loop conformation during IKs gating, while the other three, in S6 and helix A, undergo dynamic helix-loop transitions during IKs gating. These structural rearrangements: (1) stabilize the closed pore and the conformation of the intermediate state voltage-sensing domain, thereby determining channel gating, ion permeation, and single-channel conductance; (2) enable a dual-PIP2 modulation mechanism, where one PIP2 occupies the canonical site, while the second PIP2 bridges the S4-S5 linker, KCNE1, and the adjacent S6', stabilizing channel opening; (3) create a fenestration capable of binding compounds specific for KCNQ1 + KCNE1 (e.g., AC-1). Together, these findings reveal a previously unrecognized large-scale secondary structural transition during ion channel gating that fine-tunes IKs function and provides a foundation for developing targeted LQTS therapy.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":25.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205680","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

Lineage plasticity and histological transformation: tumor histology as a spectrum. 谱系可塑性和组织学转化：肿瘤组织学作为一个光谱。

IF 44.1 1区生物学

Cell Research Pub Date : 2025-09-30 DOI: 10.1038/s41422-025-01180-x

Xiaoling Li,Eric E Gardner,Sonia Molina-Pinelo,Clare Wilhelm,Ping Mu,Álvaro Quintanal-Villalonga

{"title":"Lineage plasticity and histological transformation: tumor histology as a spectrum.","authors":"Xiaoling Li,Eric E Gardner,Sonia Molina-Pinelo,Clare Wilhelm,Ping Mu,Álvaro Quintanal-Villalonga","doi":"10.1038/s41422-025-01180-x","DOIUrl":"https://doi.org/10.1038/s41422-025-01180-x","url":null,"abstract":"Lineage plasticity, the ability of cells to transition to an alternative phenotype as a means for adaptation, is an increasingly recognized mechanism of tumor evolution and a driver of resistance to anticancer therapies. The most extensively described clinical settings impacted by such molecular phenomena include neuroendocrine transformation in androgen receptor-dependent prostate adenocarcinoma, and adenocarcinoma-to-neuroendocrine and adenocarcinoma-to-squamous transdifferentiation in epidermal growth factor receptor-driven lung adenocarcinoma, affecting 10%-20% of patients treated with targeted therapy. Recent analyses of human tumor samples and in vivo models of histological transformation have led to insights into the biology of lineage plasticity, including biomarkers predictive of high risk of transformation. However, no clinically available therapies aimed to prevent or revert plasticity are currently available. In the present review, we will provide a biological and therapeutic overview of the current understanding of common and divergent molecular drivers of neuroendocrine and squamous transdifferentiation in tumors from different origins, including descriptive analysis of previously known and recently described molecular events associated with histological transformation, and propose evidence-based alternative models of transdifferentiation. A clear definition of the commonalities and differences of transforming tumors in different organs and to different histological fates will be important to translate molecular findings to the clinical setting.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"94 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189203","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 basis of vitamin K-dependent protein γ-glutamyl carboxylation. 维生素k依赖蛋白γ-谷氨酰羧化的分子基础。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-29 DOI: 10.1038/s41422-025-01185-6

Qihang Zhong, Dandan Chen, Jinkun Xu, Yao Li, Wanqiong Yuan, Yan Meng, Qi Wen, Qiwei Ye, Guopeng Wang, Kexin Pan, Chunli Song, Lin Tao, Jie Qiao, Jing Hang

引用次数: 0

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 44.1 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 44.1 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 44.1 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":"https://doi.org/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":"29 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0