Cell Discovery最新文献_第5页

TPM4 condensates glycolytic enzymes and facilitates actin reorganization under hyperosmotic stress. TPM4在高渗胁迫下凝聚糖酵解酶，促进肌动蛋白重组。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-12-03 DOI: 10.1038/s41421-024-00744-2

Wenzhong Yang, Yuan Wang, Geyao Liu, Yan Wang, Congying Wu

{"title":"TPM4 condensates glycolytic enzymes and facilitates actin reorganization under hyperosmotic stress.","authors":"Wenzhong Yang, Yuan Wang, Geyao Liu, Yan Wang, Congying Wu","doi":"10.1038/s41421-024-00744-2","DOIUrl":"10.1038/s41421-024-00744-2","url":null,"abstract":"Actin homeostasis is fundamental for cell structure and consumes a large portion of cellular ATP. It has been documented in the literature that certain glycolytic enzymes can interact with actin, indicating an intricate interplay between the cytoskeleton and cellular metabolism. Here we report that hyperosmotic stress triggers actin severing and subsequent phase separation of the actin-binding protein tropomyosin 4 (TPM4). TPM4 condensates recruit glycolytic enzymes such as HK2, PFKM, and PKM2, while wetting actin filaments. Notably, the condensates of TPM4 and glycolytic enzymes are enriched of NADH and ATP, suggestive of their functional importance in cell metabolism. At cellular level, actin filament assembly is enhanced upon hyperosmotic stress and TPM4 condensation, while depletion of TPM4 impairs osmolarity-induced actin reorganization. At tissue level, colocalized condensates of TPM4 and glycolytic enzymes are observed in renal tissues subjected to hyperosmotic stress. Together, our findings suggest that stress-induced actin perturbation may act on TPM4 to organize glycolytic hubs that tether energy production to cytoskeletal reorganization.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"120"},"PeriodicalIF":13.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766583","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

Genetic recording of transient endothelial activation in distinct alveolar capillary cells during pulmonary fibrosis. 肺纤维化过程中不同肺泡毛细血管细胞短暂内皮活化的基因记录。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-12-03 DOI: 10.1038/s41421-024-00745-1

Hongxin Li, Shaohua Zhang, Xiuzhen Huang, Zhenqian Zhang, Kuo Liu, Qing-Dong Wang, Alex F Chen, Kathy O Lui, Kun Sun, Bin Zhou

引用次数: 0

Unveiling potential threats: backdoor attacks in single-cell pre-trained models. 揭示潜在威胁：单细胞预训练模型中的后门攻击。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-30 DOI: 10.1038/s41421-024-00753-1

Sicheng Feng, Siyu Li, Luonan Chen, Shengquan Chen

引用次数: 0

Structural insights into physiological activation and antagonism of melanin-concentrating hormone receptor MCHR1. 黑色素浓缩激素受体MCHR1的生理激活和拮抗的结构见解。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-30 DOI: 10.1038/s41421-024-00754-0

Xiaofan Ye, Guibing Liu, Xiu Li, Binbin He, Yuyong Tao, Jiasheng Guan, Yuguang Mu, Haiping Liu, Weimin Gong

引用次数: 0

Structural and molecular basis of the epistasis effect in enhanced affinity between SARS-CoV-2 KP.3 and ACE2. SARS-CoV-2 KP.3与ACE2亲和力增强的上位效应的结构和分子基础

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-30 DOI: 10.1038/s41421-024-00752-2

Leilei Feng, Zhaoxi Sun, Yuchen Zhang, Fanchong Jian, Sijie Yang, Keely Xia, Lingling Yu, Jing Wang, Fei Shao, Xiangxi Wang, Yunlong Cao

引用次数: 0

Structural mechanisms of human sodium-coupled high-affinity choline transporter CHT1. 人类钠偶联高亲和性胆碱转运体 CHT1 的结构机制。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-26 DOI: 10.1038/s41421-024-00731-7

Jing Xue, Hongwen Chen, Yong Wang, Youxing Jiang

{"title":"Structural mechanisms of human sodium-coupled high-affinity choline transporter CHT1.","authors":"Jing Xue, Hongwen Chen, Yong Wang, Youxing Jiang","doi":"10.1038/s41421-024-00731-7","DOIUrl":"10.1038/s41421-024-00731-7","url":null,"abstract":"Mammalian sodium-coupled high-affinity choline transporter CHT1 uptakes choline in cholinergic neurons for acetylcholine synthesis and plays a critical role in cholinergic neurotransmission. Here, we present the high-resolution cryo-EM structures of human CHT1 in apo, substrate- and ion-bound, hemicholinium-3-inhibited, and ML352-inhibited states. These structures represent three distinct conformational states, elucidating the structural basis of the CHT1-mediated choline uptake mechanism. Three ion-binding sites, two for Na+ and one for Cl-, are unambiguously defined in the structures, demonstrating that both ions are indispensable cofactors for high-affinity choline-binding and are likely transported together with the substrate in a 2:1:1 stoichiometry. The two inhibitor-bound CHT1 structures reveal two distinct inhibitory mechanisms and provide a potential structural platform for designing therapeutic drugs to manipulate cholinergic neuron activity. Combined with the functional analysis, this study provides a comprehensive view of the structural mechanisms underlying substrate specificity, substrate/ion co-transport, and drug inhibition of a physiologically important symporter.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"116"},"PeriodicalIF":13.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715556","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

Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression. 对瘤内微生物群的特征描述显示，血管链球菌会增加胃癌发生和发展的风险。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-26 DOI: 10.1038/s41421-024-00746-0

Li Yuan, Libin Pan, Yunzhe Wang, Jing Zhao, Luo Fang, Ying Zhou, Ruihong Xia, Yubo Ma, Zhengchen Jiang, Zhiyuan Xu, Can Hu, Yanan Wang, Shengjie Zhang, Bo Zhang, Haiying Ding, Mengxuan Chen, Haibo Cheng, Ajay Goel, Zhao Zhang, Xiangdong Cheng

{"title":"Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression.","authors":"Li Yuan, Libin Pan, Yunzhe Wang, Jing Zhao, Luo Fang, Ying Zhou, Ruihong Xia, Yubo Ma, Zhengchen Jiang, Zhiyuan Xu, Can Hu, Yanan Wang, Shengjie Zhang, Bo Zhang, Haiying Ding, Mengxuan Chen, Haibo Cheng, Ajay Goel, Zhao Zhang, Xiangdong Cheng","doi":"10.1038/s41421-024-00746-0","DOIUrl":"10.1038/s41421-024-00746-0","url":null,"abstract":"As a critical component of the tumour immune microenvironment (TIME), the resident microbiota promotes tumorigenesis across a variety of cancer types. Here, we integrated multiple types of omics data, including microbiome, transcriptome, and metabolome data, to investigate the functional role of intratumoral bacteria in gastric cancer (GC). The microbiome was used to categorize GC samples into six subtypes, and patients with a high abundance of Streptococcus or Pseudomonas had a markedly worse prognosis. Further assays revealed that Streptococcus anginosus (SA) promoted tumour cell proliferation and metastasis while suppressing the differentiation and infiltration of CD8+ T cells. However, antibiotic treatment significantly suppressed tumorigenesis in SA+ mice in vivo. We further demonstrated that the SA arginine pathway increased the abundance of ornithine, which may be a major contributor to reshaping of the TIME. Our findings demonstrated that SA, a novel risk factor, plays significant roles in the initiation and progression of GC, suggesting that SA might be a promising target for the diagnosis and treatment of GC.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"117"},"PeriodicalIF":13.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715554","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

Cryo-EM structure of PML RBCC dimer reveals CC-mediated octopus-like nuclear body assembly mechanism. PML RBCC 二聚体的低温电子显微镜结构揭示了 CC 介导的章鱼状核体组装机制。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-25 DOI: 10.1038/s41421-024-00735-3

Yangxia Tan, Jiawei Li, Shiyan Zhang, Yonglei Zhang, Zhiyi Zhuo, Xiaodan Ma, Yue Yin, Yanling Jiang, Yao Cong, Guoyu Meng

{"title":"Cryo-EM structure of PML RBCC dimer reveals CC-mediated octopus-like nuclear body assembly mechanism.","authors":"Yangxia Tan, Jiawei Li, Shiyan Zhang, Yonglei Zhang, Zhiyi Zhuo, Xiaodan Ma, Yue Yin, Yanling Jiang, Yao Cong, Guoyu Meng","doi":"10.1038/s41421-024-00735-3","DOIUrl":"10.1038/s41421-024-00735-3","url":null,"abstract":"Promyelocytic leukemia protein (PML) nuclear bodies (NBs) are essential in regulating tumor suppression, antiviral response, inflammation, metabolism, aging, and other important life processes. The re-assembly of PML NBs might lead to an ~100% cure of acute promyelocytic leukemia. However, until now, the molecular mechanism underpinning PML NB biogenesis remains elusive due to the lack of structural information. In this study, we present the cryo-electron microscopy (cryo-EM) structure of the PML dimer at an overall resolution of 5.3 Å, encompassing the RING, B-box1/2 and part of the coiled-coil (RBCC) domains. The integrated approach, combining crosslinking and mass spectrometry (XL-MS) and functional analyses, enabled us to observe a unique folding event within the RBCC domains. The RING and B-box1/2 domains fold around the α3 helix, and the α6 helix serves as a pivotal interface for PML dimerization. More importantly, further characterizations of the cryo-EM structure in conjugation with AlphaFold2 prediction, XL-MS, and NB formation assays, help unveil an unprecedented octopus-like mechanism in NB assembly, wherein each CC helix of a PML dimer (PML dimer A) interacts with a CC helix from a neighboring PML dimer (PML dimer B) in an anti-parallel configuration, ultimately leading to the formation of a 2 µm membrane-less subcellular organelle.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"118"},"PeriodicalIF":13.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715555","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

Sodium oligomannate disrupts the adherence of Rib^high bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD transgenic mice. 在 5XFAD 转基因小鼠体内，低聚甘露酸钠能破坏 Ribhigh 细菌对肠道上皮的粘附，从而阻止 SAA 引发的 Th1 炎症。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-19 DOI: 10.1038/s41421-024-00725-5

Xinyi Wang, Zuoquan Xie, Jie Yuan, Enjing Jin, Wen Lian, Shuaishuai Chang, Guangqiang Sun, Zhengnan Feng, Hui Xu, Chen Du, Xinying Yang, Aihua Xia, Ji Qiu, Qingli Zhang, Feifei Lin, Jia Liu, Liang Li, Xiaoguang Du, Zhongping Xiao, Zhou Yi, Zhiyu Luo, Changrong Ge, Rui Li, Mingyue Zheng, Yi Jiang, Tao Wang, Jing Zhang, Qihao Guo, Meiyu Geng

{"title":"Sodium oligomannate disrupts the adherence of Ribhigh bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD transgenic mice.","authors":"Xinyi Wang, Zuoquan Xie, Jie Yuan, Enjing Jin, Wen Lian, Shuaishuai Chang, Guangqiang Sun, Zhengnan Feng, Hui Xu, Chen Du, Xinying Yang, Aihua Xia, Ji Qiu, Qingli Zhang, Feifei Lin, Jia Liu, Liang Li, Xiaoguang Du, Zhongping Xiao, Zhou Yi, Zhiyu Luo, Changrong Ge, Rui Li, Mingyue Zheng, Yi Jiang, Tao Wang, Jing Zhang, Qihao Guo, Meiyu Geng","doi":"10.1038/s41421-024-00725-5","DOIUrl":"10.1038/s41421-024-00725-5","url":null,"abstract":"Sodium oligomannate (GV-971), an oligosaccharide drug approved in China for treating mild-to-moderate Alzheimer's disease (AD), was previously found to recondition the gut microbiota and limit altered peripheral Th1 immunity in AD transgenic mice. As a follow-up study, we here made advances by pinpointing a Lactobacillus murinus (L.m.) strain that highly expressed a gene encoding a putative adhesin containing Rib repeats (Ribhigh-L.m.) particularly enriched in 5XFAD transgenic mice. Mechanistically, Ribhigh-L.m. adherence to the gut epithelia upregulated fecal metabolites, among which lactate ranked as the top candidate. Excess lactate stimulated the epithelial production of serum amyloid A (SAA) in the gut via the GPR81-NFκB axis, contributing to peripheral Th1 activation. Moreover, GV-971 disrupted the adherence of Ribhigh-L.m. to gut epithelia via direct binding to Rib, which corrected the excess lactate, reduced SAA, and alleviated Th1-skewed inflammation. Together, we gained further insights into the molecular link between gut bacteria and AD progression and the mechanism of GV-971 in treating AD.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"115"},"PeriodicalIF":13.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667143","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

The -KTS isoform of Wt1 induces the transformation of Leydig cells into granulosa-like cells. Wt1 的 -KTS 异构体诱导 Leydig 细胞转变为颗粒样细胞。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-12 DOI: 10.1038/s41421-024-00732-6

Changhuo Cen, Bowen Liu, Limei Lin, Zhiming Shen, Nan Wang, Liangjun Zhang, Kai Meng, Min Chen, Fei Gao

引用次数: 0