Cell Research最新文献_第8页

Localized, highly efficient secretion of signaling proteins by migrasomes 迁移体局部高效分泌信号蛋白

IF 28.1 1区生物学

Cell Research Pub Date : 2024-06-25 DOI: 10.1038/s41422-024-00992-7

Haifeng Jiao, Xiaopeng Li, Ying Li, Yuting Guo, Xiaoyu Hu, Takami Sho, Yiqun Luo, Jinyu Wang, Huizhen Cao, Wanqing Du, Dong Li, Li Yu

{"title":"Localized, highly efficient secretion of signaling proteins by migrasomes","authors":"Haifeng Jiao, Xiaopeng Li, Ying Li, Yuting Guo, Xiaoyu Hu, Takami Sho, Yiqun Luo, Jinyu Wang, Huizhen Cao, Wanqing Du, Dong Li, Li Yu","doi":"10.1038/s41422-024-00992-7","DOIUrl":"10.1038/s41422-024-00992-7","url":null,"abstract":"Migrasomes, enriched with signaling molecules such as chemokines, cytokines and angiogenic factors, play a pivotal role in the spatially defined delivery of these molecules, influencing critical physiological processes including organ morphogenesis and angiogenesis. The mechanism governing the accumulation of signaling molecules in migrasomes has been elusive. In this study, we show that secretory proteins, including signaling proteins, are transported into migrasomes by secretory carriers via both the constitutive and regulated secretion pathways. During cell migration, a substantial portion of these carriers is redirected to the rear of the cell and actively transported into migrasomes, driven by the actin-dependent motor protein Myosin-5a. Once at the migrasomes, these carriers fuse with the migrasome membrane through SNARE-mediated mechanisms. Inhibiting migrasome formation significantly reduces secretion, suggesting migrasomes as a principal secretion route in migrating cells. Our findings reveal a specialized, highly localized secretion paradigm in migrating cells, conceptually paralleling the targeted neurotransmitter release observed in neuronal systems.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 8","pages":"572-585"},"PeriodicalIF":28.1,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00992-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141448159","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

ANT2: the first mammalian mitochondrial RNA transport translocon ANT2：第一个哺乳动物线粒体 RNA 转运易位子

IF 28.1 1区生物学

Cell Research Pub Date : 2024-06-24 DOI: 10.1038/s41422-024-00994-5

Huanhuan Zhu, Weiqiang Lin, Aifu Lin

引用次数: 0

Combination therapy of KRAS G12V mRNA vaccine and pembrolizumab: clinical benefit in patients with advanced solid tumors KRAS G12V mRNA疫苗与pembrolizumab的联合疗法：晚期实体瘤患者的临床获益。

IF 28.1 1区生物学

Cell Research Pub Date : 2024-06-24 DOI: 10.1038/s41422-024-00990-9

Xinjing Wang, Wei Wang, Siyi Zou, Zhiwei Xu, Dan Cao, Shuai Zhang, Minzhi Wei, Qian Zhan, Chenlei Wen, Fanlu Li, Hao Chen, Da Fu, Lingxi Jiang, Ming Zhao, Baiyong Shen

引用次数: 0

AMPK targets PDZD8 to trigger carbon source shift from glucose to glutamine AMPK 以 PDZD8 为靶标，触发碳源从葡萄糖向谷氨酰胺的转移。

IF 28.1 1区生物学

Cell Research Pub Date : 2024-06-19 DOI: 10.1038/s41422-024-00985-6

Mengqi Li, Yu Wang, Xiaoyan Wei, Wei-Feng Cai, Jianfeng Wu, Mingxia Zhu, Yongliang Wang, Yan-Hui Liu, Jinye Xiong, Qi Qu, Yan Chen, Xiao Tian, Luming Yao, Renxiang Xie, Xiaomin Li, Siwei Chen, Xi Huang, Cixiong Zhang, Changchuan Xie, Yaying Wu, Zheni Xu, Baoding Zhang, Bin Jiang, Zhi-Chao Wang, Qinxi Li, Gang Li, Shu-Yong Lin, Li Yu, Hai-Long Piao, Xianming Deng, Jiahuai Han, Chen-Song Zhang, Sheng-Cai Lin

{"title":"AMPK targets PDZD8 to trigger carbon source shift from glucose to glutamine","authors":"Mengqi Li, Yu Wang, Xiaoyan Wei, Wei-Feng Cai, Jianfeng Wu, Mingxia Zhu, Yongliang Wang, Yan-Hui Liu, Jinye Xiong, Qi Qu, Yan Chen, Xiao Tian, Luming Yao, Renxiang Xie, Xiaomin Li, Siwei Chen, Xi Huang, Cixiong Zhang, Changchuan Xie, Yaying Wu, Zheni Xu, Baoding Zhang, Bin Jiang, Zhi-Chao Wang, Qinxi Li, Gang Li, Shu-Yong Lin, Li Yu, Hai-Long Piao, Xianming Deng, Jiahuai Han, Chen-Song Zhang, Sheng-Cai Lin","doi":"10.1038/s41422-024-00985-6","DOIUrl":"10.1038/s41422-024-00985-6","url":null,"abstract":"The shift of carbon utilization from primarily glucose to other nutrients is a fundamental metabolic adaptation to cope with decreased blood glucose levels and the consequent decline in glucose oxidation. AMP-activated protein kinase (AMPK) plays crucial roles in this metabolic adaptation. However, the underlying mechanism is not fully understood. Here, we show that PDZ domain containing 8 (PDZD8), which we identify as a new substrate of AMPK activated in low glucose, is required for the low glucose-promoted glutaminolysis. AMPK phosphorylates PDZD8 at threonine 527 (T527) and promotes the interaction of PDZD8 with and activation of glutaminase 1 (GLS1), a rate-limiting enzyme of glutaminolysis. In vivo, the AMPK-PDZD8-GLS1 axis is required for the enhancement of glutaminolysis as tested in the skeletal muscle tissues, which occurs earlier than the increase in fatty acid utilization during fasting. The enhanced glutaminolysis is also observed in macrophages in low glucose or under acute lipopolysaccharide (LPS) treatment. Consistent with a requirement of heightened glutaminolysis, the PDZD8-T527A mutation dampens the secretion of pro-inflammatory cytokines in macrophages in mice treated with LPS. Together, we have revealed an AMPK-PDZD8-GLS1 axis that promotes glutaminolysis ahead of increased fatty acid utilization under glucose shortage.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 10","pages":"683-706"},"PeriodicalIF":28.1,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00985-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426455","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

Pyroptosis: palmitoylation regulates GSDMD activation and pore formation 裂解：棕榈酰化调节 GSDMD 的激活和孔隙形成

IF 28.1 1区生物学

Cell Research Pub Date : 2024-06-18 DOI: 10.1038/s41422-024-00988-3

Ella Hartenian, Petr Broz

引用次数: 0

AI accurately predicting the structure of biomolecular interactions 人工智能准确预测生物分子相互作用的结构。

IF 28.1 1区生物学

Cell Research Pub Date : 2024-06-14 DOI: 10.1038/s41422-024-00991-8

Zhenling Peng, Peilong Lu, Jianyi Yang

引用次数: 0

Structural insights into VAChT neurotransmitter recognition and inhibition 有关 VAChT 神经递质识别和抑制的结构见解

IF 28.1 1区生物学

Cell Research Pub Date : 2024-06-11 DOI: 10.1038/s41422-024-00986-5

Yang Zhang, Fei Dai, Nanhao Chen, Dong Zhou, Chia-Hsueh Lee, Chen Song, Yixiao Zhang, Zhe Zhang

引用次数: 0

Tumor microenvironment squeezes out the juice from T cells 肿瘤微环境榨干了 T 细胞的汁液

IF 28.1 1区生物学

Cell Research Pub Date : 2024-06-10 DOI: 10.1038/s41422-024-00987-4

Romane Thouenon, Grégory Verdeil

引用次数: 0

A GABAergic system in atrioventricular node pacemaker cells controls electrical conduction between the atria and ventricles 房室结起搏细胞中的 GABA 能系统控制着心房和心室之间的电传导

IF 28.1 1区生物学

Cell Research Pub Date : 2024-06-07 DOI: 10.1038/s41422-024-00980-x

Dandan Liang, Liping Zhou, Huixing Zhou, Fulei Zhang, Guojian Fang, Junwei Leng, Yahan Wu, Yuemei Zhang, Anqi Yang, Yi Liu, Yi-Han Chen

{"title":"A GABAergic system in atrioventricular node pacemaker cells controls electrical conduction between the atria and ventricles","authors":"Dandan Liang, Liping Zhou, Huixing Zhou, Fulei Zhang, Guojian Fang, Junwei Leng, Yahan Wu, Yuemei Zhang, Anqi Yang, Yi Liu, Yi-Han Chen","doi":"10.1038/s41422-024-00980-x","DOIUrl":"10.1038/s41422-024-00980-x","url":null,"abstract":"Physiologically, the atria contract first, followed by the ventricles, which is the prerequisite for normal blood circulation. The above phenomenon of atrioventricular sequential contraction results from the characteristically slow conduction of electrical excitation of the atrioventricular node (AVN) between the atria and the ventricles. However, it is not clear what controls the conduction of electrical excitation within AVNs. Here, we find that AVN pacemaker cells (AVNPCs) possess an intact intrinsic GABAergic system, which plays a key role in electrical conduction from the atria to the ventricles. First, along with the discovery of abundant GABA-containing vesicles under the surface membranes of AVNPCs, key elements of the GABAergic system, including GABA metabolic enzymes, GABA receptors, and GABA transporters, were identified in AVNPCs. Second, GABA synchronously elicited GABA-gated currents in AVNPCs, which significantly weakened the excitability of AVNPCs. Third, the key molecular elements of the GABAergic system markedly modulated the conductivity of electrical excitation in the AVN. Fourth, GABAA receptor deficiency in AVNPCs accelerated atrioventricular conduction, which impaired the AVN’s protective potential against rapid ventricular frequency responses, increased susceptibility to lethal ventricular arrhythmias, and decreased the cardiac contractile function. Finally, interventions targeting the GABAergic system effectively prevented the occurrence and development of atrioventricular block. In summary, the endogenous GABAergic system in AVNPCs determines the slow conduction of electrical excitation within AVNs, thereby ensuring sequential atrioventricular contraction. The endogenous GABAergic system shows promise as a novel intervention target for cardiac arrhythmias.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 8","pages":"556-571"},"PeriodicalIF":28.1,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00980-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287092","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

Molecular and structural basis of an ATPase-nuclease dual-enzyme anti-phage defense complex ATP酶-核酸酶双酶抗噬菌体防御复合物的分子和结构基础。

IF 28.1 1区生物学

Cell Research Pub Date : 2024-06-04 DOI: 10.1038/s41422-024-00981-w

Qiyin An, Yong Wang, Zhenhua Tian, Jie Han, Jinyue Li, Fumeng Liao, Feiyang Yu, Haiyan Zhao, Yancheng Wen, Heng Zhang, Zengqin Deng

{"title":"Molecular and structural basis of an ATPase-nuclease dual-enzyme anti-phage defense complex","authors":"Qiyin An, Yong Wang, Zhenhua Tian, Jie Han, Jinyue Li, Fumeng Liao, Feiyang Yu, Haiyan Zhao, Yancheng Wen, Heng Zhang, Zengqin Deng","doi":"10.1038/s41422-024-00981-w","DOIUrl":"10.1038/s41422-024-00981-w","url":null,"abstract":"Coupling distinct enzymatic effectors emerges as an efficient strategy for defense against phage infection in bacterial immune responses, such as the widely studied nuclease and cyclase activities in the type III CRISPR-Cas system. However, concerted enzymatic activities in other bacterial defense systems are poorly understood. Here, we biochemically and structurally characterize a two-component defense system DUF4297–HerA, demonstrating that DUF4297–HerA confers resistance against phage infection by cooperatively cleaving dsDNA and hydrolyzing ATP. DUF4297 alone forms a dimer, and HerA alone exists as a nonplanar split spiral hexamer, both of which exhibit extremely low enzymatic activity. Interestingly, DUF4297 and HerA assemble into an approximately 1 MDa supramolecular complex, where two layers of DUF4297 (6 DUF4297 molecules per layer) linked via inter-layer dimerization of neighboring DUF4297 molecules are stacked on top of the HerA hexamer. Importantly, the complex assembly promotes dimerization of DUF4297 molecules in the upper layer and enables a transition of HerA from a nonplanar hexamer to a planar hexamer, thus activating their respective enzymatic activities to abrogate phage infection. Together, our findings not only characterize a novel dual-enzyme anti-phage defense system, but also reveal a unique activation mechanism by cooperative complex assembly in bacterial immunity.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 8","pages":"545-555"},"PeriodicalIF":28.1,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247608","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