Editorial Material
Biochemistry & Molecular Biology
Leonie Unterholzner
Summary: The DNA sensor cGAS and its adaptor STING form an ancient pathogen detection mechanism, but its conservation across the animal kingdom is uncertain. In this article in Cell, Kranzusch and colleagues identify numerous cGAS-like receptors and uncover networks of second messengers that activate innate immune responses in animals.
Article
Physiology
Mikel Rezola, Aida Castellanos, Xavier Gasull, Nuria Comes
Summary: VRAC, a crucial channel in vertebrate cell volume homeostasis, can be activated by factors such as cell swelling. Evidence shows a physical interaction between key subunit LRRC8A and Cav1 proteins, suggesting a role of Cav1 in modulating VRAC activity.
FRONTIERS IN PHYSIOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Shubhanjali Minhas, Alex S. Holehouse
Summary: The study reveals a conserved viral mechanism in which herpesvirus tegument proteins suppress cGAS:DNA phase separation, thereby subverting the innate immune system.
Review
Pharmacology & Pharmacy
Go Kasuya, Osamu Nureki
Summary: Members of the LRRC8 protein family, as the pore-forming components of VRAC, play a critical role in regulating cell swelling by releasing chloride ions or other osmolytes. Recent advances in cryo-EM have provided valuable insights into the molecular mechanisms of LRRC8, including its overall architectures and the mechanisms underlying pore inhibition and allosteric modulation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Youzhou Tang, Xinyu Li, Yafang Wei, Yongchao Sun, Yeyi Yang, Xianming Zhang, Zhihao Gao, Jishi Liu, Quan Zhuang
Summary: This study identified significant differential expression of eight acetyltransferase and deacetylase family members in SLE, with KAT2A being upregulated and positively correlated with disease activity index. KAT2A was found to modulate cGAS pathway through increasing expression and post-translational modification, specifically in certain immune cell subsets in SLE.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Heng Liu, Maya M. Polovitskaya, Linlin Yang, Meiling Li, Hongyu Li, Zhen Han, Jianguo Wu, Qiansen Zhang, Thomas J. Jentsch, Jun Liao
Summary: This study reports the 3D structure of human LRRC8A, which can regulate cell volume regulation and ion selectivity, and proposes a mechanism for VRAC activation.
Article
Chemistry, Physical
Jordi Soler, Pedro Paiva, Maria J. Ramos, Pedro A. Fernandes, Marie Brut
Summary: This study utilizes Molecular Dynamics to investigate the activation of cGAS, focusing on the motion of the activation loop and its role in cGAMP production. Insights into the reaction resulting in cGAMP synthesis are provided, with two possible catalytic routes proposed based on active site occupancy. This paves the way towards further exploration of the reaction mechanism.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Chemistry, Medicinal
Zheng-Yu Jiang, Qi-Dong You, Xiao-Li Xu, Nan-Nan Chen, Han Zhang, Qiang-Sheng Zhu, Ting Zeng, Wei Dai, Ye-Ling Zhou, Guo-Feng Xin, Bei-Duo Wu, Si-Jia Gong
Summary: By modifying and optimizing the structure of mono-aminobenzimidazole (ABZI), nanomolar STING agonists were obtained. Compounds D59 and D61 significantly increased the transcription of IFN-beta and CXCL10, and induced phosphorylation of STING downstream proteins in THP1 cells. Furthermore, compound D61 exhibited favorable pharmacokinetic properties and effectively inhibited tumor growth in a mouse tumor model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Dawid Deneka, Sonja Rutz, Cedric A. J. Hutter, Markus A. Seeger, Marta Sawicka, Raimund Dutzler
Summary: In this study, nanobodies targeting the LRR domain of LRRC8A have been developed and characterized, providing specific modulators for LRRC8 proteins and revealing the role of their cytoplasmic domains in regulating channel activity through allosteric mechanisms. Cryo-electron microscopy and electrophysiology experiments showed that these nanobodies can alter LRRC8A channel activity by binding to distinct epitopes of the LRR domain and changing channel conformations.
NATURE COMMUNICATIONS
(2021)
Review
Chemistry, Multidisciplinary
Manzoor Ahmad, Shaun A. A. Gartland, Matthew J. J. Langton
Summary: Synthetic supramolecular ion transporters have diverse applications, including as potential therapeutics and tools for engineering functional membranes. This Minireview provides an overview of current approaches to developing stimuli-responsive ion transport systems, such as channels and mobile carriers, that can be controlled using photo or redox inputs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Yineng Han, Qiaolin Yang, Yiping Huang, Pengfei Gao, Lingfei Jia, Yunfei Zheng, Weiran Li
Summary: Compressive force regulates orthodontic tooth movement by activating the NLRP3 inflammasome and inhibiting autophagy.
Article
Biology
Yakun Wu, Kun Song, Wenzhuo Hao, Jack Li, Lingyan Wang, Shitao Li
Summary: This study demonstrates that HSV-1 infection causes the release of cGAS from the chromatin into the nuclear soluble fraction. The nuclear soluble cGAS acts as a nuclear DNA sensor and can detect nuclear-replicating DNA viruses, leading to an interferon response and limiting viral infection.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Junheng Zhao, Song Peng, Hongtu Cui, Panyu Li, Tianming Li, Luole Liu, Hanfeng Zhang, Zengyuan Tian, Haihong Shang, Ruqiang Xu
Summary: This study comprehensively identified and characterized CNGCs in cotton, revealing their expression patterns, regulatory mechanisms, and functional diversity. The findings lay the foundation for further research and utilization of CNGCs in cotton genetic improvement.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Manolia R. Ghouli, Todd A. Fiacco, Devin K. Binder
Summary: Volume Regulated Anion Channels (VRAC) are crucial for maintaining cell volume homeostasis and are found in all vertebrate cells. They sense increases in cell volume and help cells return to their baseline volume through the efflux of anions and organic osmolytes. This review provides an overview of seminal studies on the role of VRAC in regulatory volume decrease (RVD), their characteristics based on subunit specificity, and their clinical relevance in physiology and pathology.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Laura E. Bickerton, Matthew J. Langton
Summary: This research introduces a novel mechanism for photo-gating ion carriers, which controls the mobility of carriers within the lipid bilayer membrane to achieve switchable ion transport activity. This approach does not involve direct functionalization of the ion binding site, providing a new avenue for precise control over ion carrier activity.
Article
Immunology
Shixin Ma, Xiaoling Wan, Zihou Deng, Lei Shi, Congfang Hao, Zhenyuan Zhou, Chun Zhou, Yiyuan Fang, Jinghua Liu, Jing Yang, Xia Chen, Tiantian Li, Aiping Zang, Shigang Yin, Bin Li, Joel Plumas, Laurence Chaperot, Xiaoming Zhang, Guoliang Xu, Lubin Jiang, Nan Shen, Sidong Xiong, Xiaoming Gao, Yan Zhang, Hui Xiao
JOURNAL OF EXPERIMENTAL MEDICINE
(2017)
Article
Immunology
Chun Zhou, Xia Chen, Rosa Planells-Cases, Jiachen Chu, Li Wang, Limin Cao, Zhihong Li, Karen Lopez-Cayuqueo, Yadong Xie, Shiwei Ye, Xiang Wang, Florian Ullrich, Shixin Ma, Yiyuan Fang, Xiaoming Zhang, Zhikang Qian, Xiaozheng Liang, Shi-Qing Cai, Zhengfan Jiang, Dongming Zhou, Qibin Leng, Tsan S. Xiao, Ke Lan, Jinbo Yang, Huabin Li, Chao Peng, Zhaozhu Qiu, Thomas J. Jentsch, Hui Xiao
Article
Immunology
Yadong Xie, Min Li, Kun Chen, Haoxiang Zhu, Mengyao Tang, Chun Zhou, Yaoming Zheng, Jing Wen, Miaomiao Han, Jia Zhang, Keqing Zhao, Hui Xiao, Huabin Li
Summary: The study revealed that necroptosis is prominently activated in chronic rhinosinusitis with nasal polyps (CRSwNP), with elevated phosphorylation of MLKL compared to controls. Furthermore, DAMPs, inflammatory cytokines, and chemokines were increased in non-eosinophilic CRSwNP, and the extent of necroptosis was positively correlated with the abundance of these factors as well as neutrophil infiltration. Additionally, TNF-alpha and IFN-gamma induced necroptosis in THP-1 cells, suggesting a potential role in exacerbating inflammation in CRSwNP.
JOURNAL OF INFLAMMATION RESEARCH
(2021)