Cell Research最新文献

NO-immune privilege for hematopoietic stem cells.

IF 28.1 1区生物学

Cell Research Pub Date : 2025-02-28 DOI: 10.1038/s41422-025-01087-7

Agathe L Chédeville, Simón Méndez-Ferrer

引用次数: 0

Structural insights into spliceosome fidelity: DHX35-GPATCH1- mediated rejection of aberrant splicing substrates. 剪接体保真度的结构洞察：DHX35-GPATCH1介导的对异常剪接底物的排斥。

IF 28.1 1区生物学

Cell Research Pub Date : 2025-02-28 DOI: 10.1038/s41422-025-01084-w

Yi Li, Paulina Fischer, Mengjiao Wang, Qianxing Zhou, Aixia Song, Rui Yuan, Wanyu Meng, Fei Xavier Chen, Reinhard Lührmann, Benjamin Lau, Ed Hurt, Jingdong Cheng

{"title":"Structural insights into spliceosome fidelity: DHX35-GPATCH1- mediated rejection of aberrant splicing substrates.","authors":"Yi Li, Paulina Fischer, Mengjiao Wang, Qianxing Zhou, Aixia Song, Rui Yuan, Wanyu Meng, Fei Xavier Chen, Reinhard Lührmann, Benjamin Lau, Ed Hurt, Jingdong Cheng","doi":"10.1038/s41422-025-01084-w","DOIUrl":"10.1038/s41422-025-01084-w","url":null,"abstract":"The spliceosome, a highly dynamic macromolecular assembly, catalyzes the precise removal of introns from pre-mRNAs. Recent studies have provided comprehensive structural insights into the step-wise assembly, catalytic splicing and final disassembly of the spliceosome. However, the molecular details of how the spliceosome recognizes and rejects suboptimal splicing substrates remained unclear. Here, we show cryo-electron microscopy structures of spliceosomal quality control complexes from a thermophilic eukaryote, Chaetomium thermophilum. The spliceosomes, henceforth termed B*Q, are stalled at a catalytically activated state but prior to the first splicing reaction due to an aberrant 5' splice site conformation. This state is recognized by G-patch protein GPATCH1, which is docked onto PRP8-EN and -RH domains and has recruited the cognate DHX35 helicase to its U2 snRNA substrate. In B*Q, DHX35 has dissociated the U2/branch site helix, while the disassembly helicase DHX15 is docked close to its U6 RNA 3'-end substrate. Our work thus provides mechanistic insights into the concerted action of two spliceosomal helicases in maintaining splicing fidelity by priming spliceosomes that are bound to aberrant splice substrates for disassembly.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522758","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 phosphate export by human XPR1.

IF 28.1 1区生物学

Cell Research Pub Date : 2025-02-28 DOI: 10.1038/s41422-025-01081-z

Yifei Wang, Yuechan Wang, Hui Yang, Ao Li, Dan Ma, Huaizong Shen

引用次数: 0

Author Correction: The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb. 作者更正：快速近似标记系统 PhastID 将 ATP6AP1 鉴定为 Rheb 的非传统 GEF。

IF 28.1 1区生物学

Cell Research Pub Date : 2025-02-28 DOI: 10.1038/s41422-025-01088-6

Ran Feng, Feng Liu, Ruofei Li, Zhifen Zhou, Zhuoheng Lin, Song Lin, Shengcheng Deng, Yingying Li, Baoting Nong, Ying Xia, Zhiyi Li, Xiaoqin Zhong, Shuhan Yang, Gang Wan, Wenbin Ma, Su Wu, Zhou Songyang

引用次数: 0

TCR catch bonds nonlinearly control CD8 cooperation to shape T cell specificity.

IF 28.1 1区生物学

Cell Research Pub Date : 2025-02-27 DOI: 10.1038/s41422-025-01077-9

Rui Qin, Yong Zhang, Jiawei Shi, Peng Wu, Chenyi An, Zhenhai Li, Nuo Liu, Ziyan Wan, Ting Hua, Xiaolong Li, Jizhong Lou, Weiwei Yin, Wei Chen

{"title":"TCR catch bonds nonlinearly control CD8 cooperation to shape T cell specificity.","authors":"Rui Qin, Yong Zhang, Jiawei Shi, Peng Wu, Chenyi An, Zhenhai Li, Nuo Liu, Ziyan Wan, Ting Hua, Xiaolong Li, Jizhong Lou, Weiwei Yin, Wei Chen","doi":"10.1038/s41422-025-01077-9","DOIUrl":"https://doi.org/10.1038/s41422-025-01077-9","url":null,"abstract":"Naturally evolved T-cell receptors (TCRs) exhibit remarkably high specificity in discriminating non-self antigens from self-antigens under dynamic biomechanical modulation. In contrast, engineered high-affinity TCRs often lose this specificity, leading to cross-reactivity with self-antigens and off-target toxicity. The underlying mechanism for this difference remains unclear. Our study reveals that natural TCRs exploit mechanical force to form optimal catch bonds with their cognate antigens. This process relies on a mechanically flexible TCR-pMHC binding interface, which enables force-enhanced CD8 coreceptor binding to MHC-α1α2 domains through sequential conformational changes induced by force in both the MHC and CD8. Conversely, engineered high-affinity TCRs create rigid, tightly bound interfaces with cognate pMHCs of their parental TCRs. This rigidity prevents the force-induced conformational changes necessary for optimal catch-bond formation. Paradoxically, these high-affinity TCRs can form moderate catch bonds with non-stimulatory pMHCs of their parental TCRs, leading to off-target cross-reactivity and reduced specificity. We have also developed comprehensive force-dependent TCR-pMHC kinetics-function maps capable of distinguishing functional and non-functional TCR-pMHC pairs and identifying toxic, cross-reactive TCRs. These findings elucidate the mechano-chemical basis of the specificity of natural TCRs and highlight the critical role of CD8 in targeting cognate antigens. This work provides valuable insights for engineering TCRs with enhanced specificity and potency against non-self antigens, particularly for applications in cancer immunotherapy and infectious disease treatment, while minimizing the risk of self-antigen cross-reactivity.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514836","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

Hangry hairs: intermittent fasting linked to hair loss

IF 44.1 1区生物学

Cell Research Pub Date : 2025-02-25 DOI: 10.1038/s41422-025-01082-y

Carlos Galvan, William E. Lowry

引用次数: 0

Mimicking the TCR immune synapse for improved CAR-T cell function

IF 44.1 1区生物学

Cell Research Pub Date : 2025-02-25 DOI: 10.1038/s41422-025-01086-8

Tom Enbar, Li Tang

引用次数: 0

Grease, fuel and target — polyunsaturated lipids in metastasis

IF 44.1 1区生物学

Cell Research Pub Date : 2025-02-25 DOI: 10.1038/s41422-025-01089-5

Annemarie Schwab, Thomas Brabletz

引用次数: 0

A force-sensitive adhesion GPCR is required for equilibrioception

IF 44.1 1区生物学

Cell Research Pub Date : 2025-02-18 DOI: 10.1038/s41422-025-01075-x

Zhao Yang, Shu-Hua Zhou, Qi-Yue Zhang, Zhi-Chen Song, Wen-Wen Liu, Yu Sun, Ming-Wei Wang, Xiao-Long Fu, Kong-Kai Zhu, Ying Guan, Jie-Yu Qi, Xiao-Hui Wang, Yu-Nan Sun, Yan Lu, Yu-Qi Ping, Yue-Tong Xi, Zhen-Xiao Teng, Lei Xu, Peng Xiao, Zhi-Gang Xu, Wei Xiong, Wei Qin, Wei Yang, Fan Yi, Ren-Jie Chai, Xiao Yu, Jin-Peng Sun

{"title":"A force-sensitive adhesion GPCR is required for equilibrioception","authors":"Zhao Yang, Shu-Hua Zhou, Qi-Yue Zhang, Zhi-Chen Song, Wen-Wen Liu, Yu Sun, Ming-Wei Wang, Xiao-Long Fu, Kong-Kai Zhu, Ying Guan, Jie-Yu Qi, Xiao-Hui Wang, Yu-Nan Sun, Yan Lu, Yu-Qi Ping, Yue-Tong Xi, Zhen-Xiao Teng, Lei Xu, Peng Xiao, Zhi-Gang Xu, Wei Xiong, Wei Qin, Wei Yang, Fan Yi, Ren-Jie Chai, Xiao Yu, Jin-Peng Sun","doi":"10.1038/s41422-025-01075-x","DOIUrl":"https://doi.org/10.1038/s41422-025-01075-x","url":null,"abstract":"Equilibrioception (sensing of balance) is essential for mammals to perceive and navigate the three-dimensional world. A rapid mechanoelectrical transduction (MET) response in vestibular hair cells is crucial for detecting position and motion. Here, we identify the G protein-coupled receptor (GPCR) LPHN2/ADGRL2, expressed on the apical membrane of utricular hair cells, as essential for maintaining normal balance. Loss of LPHN2 specifically in hair cells impaired both balance behavior and the MET response in mice. Functional analyses using hair-cell-specific Lphn2-knockout mice and an LPHN2-specific inhibitor suggest that LPHN2 regulates tip-link-independent MET currents at the apical surface of utricular hair cells. Mechanistic studies in a heterologous system show that LPHN2 converts force stimuli into increased open probability of transmembrane channel-like protein 1 (TMC1). LPHN2-mediated force sensation triggers glutamate release and calcium signaling in utricular hair cells. Importantly, reintroducing LPHN2 into the hair cells of Lphn2-deficient mice restores vestibular function and MET response. Our data reveal that a mechanosensitive GPCR is required for equilibrioception.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"47 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435061","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

Raptin, a novel brain hormone links sleep health to body weight gain 新型脑激素 Raptin 将睡眠健康与体重增加联系起来

IF 44.1 1区生物学

Cell Research Pub Date : 2025-02-17 DOI: 10.1038/s41422-025-01083-x

Leonie Cabot, Henning Fenselau

引用次数: 0