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Bitter taste receptor TAS2R14 activation and G protein assembly by an intracellular agonist 苦味受体 TAS2R14 被细胞内激动剂激活和 G 蛋白组装
IF 28.1 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-07-05 DOI: 10.1038/s41422-024-00995-4
Lele Tao, Dongxue Wang, Qingning Yuan, Fenghui Zhao, Yu Zhang, Tianyuan Du, Shiyi Shen, H. Eric Xu, Yi Li, Dehua Yang, Jia Duan
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引用次数: 0
Molecular insights into the inhibition of proton-activated chloride channel by transfer RNA 转运核糖核酸抑制质子激活的氯离子通道的分子见解
IF 28.1 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-06-28 DOI: 10.1038/s41422-024-00993-6
Pengliang Chi, Xiang Wang, Jialu Li, Hui Yang, Kaiju Li, Yuqi Zhang, Shiyi Lin, Leiye Yu, Shiqi Liu, Lu Chen, Ruobing Ren, Jianping Wu, Zhuo Huang, Jia Geng, Dong Deng
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引用次数: 0
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 Q1 CELL BIOLOGY 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
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.
移行体富含趋化因子、细胞因子和血管生成因子等信号分子,在这些分子的空间传递中发挥着关键作用,影响着器官形态发生和血管生成等关键生理过程。信号分子在移行体中的积累机制一直难以捉摸。在这项研究中,我们发现分泌蛋白(包括信号蛋白)通过组成型分泌途径和调节型分泌途径被分泌载体运输到迁移体中。在细胞迁移过程中,这些载体的很大一部分被重新定向到细胞后部,并在肌动蛋白依赖性马达蛋白肌球蛋白-5a的驱动下被主动运输到迁移体中。一旦进入移行体,这些载体就会通过 SNARE 介导的机制与移行体膜融合。抑制迁移体的形成可显著减少分泌,这表明迁移体是迁移细胞的主要分泌途径。我们的研究结果揭示了迁移细胞中一种专门的、高度局部化的分泌模式,在概念上与神经元系统中观察到的定向神经递质释放相似。
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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 Q1 CELL BIOLOGY Pub Date : 2024-06-24 DOI: 10.1038/s41422-024-00994-5
Huanhuan Zhu, Weiqiang Lin, Aifu Lin
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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 Q1 CELL BIOLOGY 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
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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 Q1 CELL BIOLOGY 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
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.
碳的利用从主要利用葡萄糖转向利用其他营养物质,是应对血糖水平下降和随之而来的葡萄糖氧化下降的一种基本代谢适应。AMP 激活蛋白激酶(AMPK)在这种新陈代谢适应中起着至关重要的作用。然而,其潜在机制尚未完全明了。在这里,我们发现,PDZ 含域 8(PDZD8)是 AMPK 在低糖条件下激活的新底物,它是低糖促进谷氨酰胺溶解所必需的。AMPK 使 PDZD8 在苏氨酸 527 (T527) 处磷酸化,并促进 PDZD8 与谷氨酰胺酶 1 (GLS1) 的相互作用和激活,GLS1 是谷氨酰胺分解的限速酶。在体内,AMPK-PDZD8-GLS1 轴是增强谷氨酰胺酵解所必需的,骨骼肌组织的测试结果表明,谷氨酰胺酵解的增强早于禁食期间脂肪酸利用的增加。在低糖或急性脂多糖(LPS)处理下的巨噬细胞中也能观察到谷氨酰胺溶解的增强。PDZD8-T527A 突变抑制了经 LPS 处理的小鼠巨噬细胞中促炎细胞因子的分泌,这与谷氨酰胺分解增强的要求相一致。综上所述,我们揭示了 AMPK-PDZD8-GLS1 轴在葡萄糖不足的情况下促进谷氨酰胺酵解,而不是增加脂肪酸的利用。
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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 Q1 CELL BIOLOGY Pub Date : 2024-06-18 DOI: 10.1038/s41422-024-00988-3
Ella Hartenian, Petr Broz
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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 Q1 CELL BIOLOGY Pub Date : 2024-06-14 DOI: 10.1038/s41422-024-00991-8
Zhenling Peng, Peilong Lu, Jianyi Yang
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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 Q1 CELL BIOLOGY 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
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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 Q1 CELL BIOLOGY Pub Date : 2024-06-10 DOI: 10.1038/s41422-024-00987-4
Romane Thouenon, Grégory Verdeil
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引用次数: 0
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