Review
Oncology
Quanjin Li, Pu Gao
Summary: Biomolecular condensates formed by phase separation play critical roles in cGAS-STING signaling, including cGAS condensates, STING condensates, and IRF3 condensates. The regulation and activation mechanisms of these condensates are under investigation, offering new opportunities for drug discovery.
FRONTIERS OF MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Yuanxing Zhi, Jin Liu, Peihua Kuang, Xin Zhang, Ziwei Xu, Yanshan Chen, Xiuling Lin, Xiaoyan Wu, Pingzheng Zhou, Jianjun Chen
Summary: In this study, a series of novel DCPIB derivatives were synthesized and found to have dual inhibitory effects on VRAC/TREK1 channels. Compound 6u showed potential in inhibiting interferon production in the cGAS-cGAMP-STING pathway, without any cytotoxicity during HSV1 infection. This research provides a new strategy for the development of potent VRAC inhibitors and its potential applications in treating cGAS-STING related autoimmune and inflammatory diseases.
BIOCHEMICAL PHARMACOLOGY
(2022)
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)
Article
Immunology
Xue Qiao, Yanan Zong, Zhaoqun Liu, Zhaojun Wu, Yuanmei Li, Lingling Wang, Linsheng Song
Summary: The study revealed a primitive IFN-like antiviral mechanism in mollusks, dependent on the cGAS/STING-TBK1-IRFs regulatory axis, which differs from the classic cGAS-STING-TBK1 signal pathway in mammals.
FRONTIERS IN IMMUNOLOGY
(2021)
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)
Article
Biochemistry & Molecular Biology
Hitesh Vasiyani, Anjali Shinde, Milton Roy, Minal Mane, Kritarth Singh, Jyoti Singh, Dhruv Gohel, Fatema Currim, Khushali Vaidya, Mahesh Chhabria, Rajesh Singh
Summary: The study demonstrates that c-di-AMP can activate the type-1 IFN response in ER-negative breast cancer cells, which is correlated with STING expression. Furthermore, c-di-AMP induces mitochondrial-mediated cell death and inhibits clonogenicity of triple-negative breast cancer cells.
Review
Biotechnology & Applied Microbiology
Zi-Jie Long, Jun-Dan Wang, Jue-Qiong Xu, Xin-Xing Lei, Quentin Liu
Summary: The accurate duplication and transfer of genetic material is crucial for cell division. The interaction between cell cycle regulation and cGAS/STING signaling plays a significant role in cancer initiation, development, and treatment.
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
Oncology
Marino Nagata, Akemi Kosaka, Yuki Yajima, Syunsuke Yasuda, Mizuho Ohara, Kenzo Ohara, Shohei Harabuchi, Ryusuke Hayashi, Hiroshi Funakoshi, Jun Ueda, Takumi Kumai, Toshihiro Nagato, Kensuke Oikawa, Yasuaki Harabuchi, Celis Esteban, Takayuki Ohkuri, Hiroya Kobayashi
Summary: The study highlights that STING activation enhances neutrophil migration into tumors through the CXCL1/2 and type I interferon signaling pathways, affecting T cell activation and anti-tumor effects. In vitro experiments also demonstrated that IFN-beta 1 can enhance the cytotoxicity of neutrophils.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
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.
Review
Oncology
Natasha Samson, Andrea Ablasser
Summary: The cGAS-STING pathway plays a critical role in cancer and can affect tumor development and treatment outcomes. This article discusses the impact of cGAS-STING signaling on tumors and highlights current research efforts in this field.
Article
Multidisciplinary Sciences
Seoyun Yum, Minghao Li, Yan Fang, Zhijian J. Chen
Summary: This study shows that STING can function independently of type I interferons and autophagy, and that TBK1 recruitment to STING is essential for antiviral and antitumor immunity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Christopher Ritchie, Jacqueline A. Carozza, Lingyin Li
Summary: This review focuses on the innate immune cyclic GMP-AMP synthase (cGAS)-2'3'-cyclic GMP-AMP (cGAMP)-stimulator of interferon genes (STING) pathway and its implications in human disease. The review discusses the synthesis of cGAMP by cGAS and the subsequent signaling cascades mediated by STING with differential physiological consequences. It also explores how cGAMP acts as an immunotransmitter and the pathways' response to mislocalized double-stranded DNA in pathogen defense, cancer, and autoimmune diseases.
ANNUAL REVIEW OF BIOCHEMISTRY
(2022)
Article
Immunology
Shishi Qi, Changwan Wang, Rui Zhang, Junyan Zhu, Xianteng Hou, Yingbo Jiang, Jiaxin Li, Miao Ren, Muwang Li, Fajian Hou
Summary: Our study uncovers a novel mechanism of human STING, showing that its C-terminal tail (CTT) can activate downstream signaling regardless of its localization in the endoplasmic reticulum (ER). Additionally, we demonstrate that the ligand-binding domain (LBD) of STING inhibits the activity of CTT and interferes with interferon production.
JOURNAL OF INNATE IMMUNITY
(2022)
Review
Urology & Nephrology
Sladjana Skopelja-Gardner, Jie An, Keith B. Elkon
Summary: Cells have sensors that recognize nucleic acids, triggering immune responses and promoting antiviral states. The cGAS-STING pathway, a recently identified DNA sensor pathway, binds DNA and produces a messenger molecule called cGAMP, leading to an inflammatory response. This pathway is involved in various diseases and has therapeutic potential.
NATURE REVIEWS NEPHROLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Florian Ullrich
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Allergy
Min Li, Jiaojiao Liu, Renfei Lu, Yuchao Zhang, Meng Du, Man Xing, Zhenchuan Wu, Xiangyin Kong, Yufei Zhu, Xianchao Zhou, Landian Hu, Chiyu Zhang, Dongming Zhou, Xia Jin
Summary: The study reveals that SARS-CoV-2 infection induces persistent humoral immunity in COVID-19 convalescent individuals by targeting dominant epitopes located at the spike and ORF1ab proteins, which mediate long-term immune responses.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Chongyuan Wang, Maya M. Polovitskaya, Bryce D. Delgado, Thomas J. Jentsch, Stephen B. Long
Summary: This study reveals the activated conformation and related mechanisms of the proton-activated chloride channel ASOR in acidic conditions. The study found that clusters of extracellular acidic residues gather and induce conformational changes, forming a specific ion conduction pathway. This research is important for understanding the gating mechanism of this ion channel.
Article
Cell Biology
Mariia Zeziulia, Sandy Blin, Franziska W. Schmitt, Martin Lehmann, Thomas J. Jentsch
Summary: Zeziulia et al. identified the proton-activated Cl- channel ASOR/TMEM206 as necessary for the shrinkage of macrophage macropinosomes, which plays a crucial role in sorting and trafficking of cellular organelles. The activation of ASOR requires depolarization mediated by Na+ and acidification by transporters such as H+-ATPases.
NATURE CELL BIOLOGY
(2022)
Article
Urology & Nephrology
Karen Lopez-Cayuqueo, Rosa Planells-Cases, Matthias Pietzke, Anna Oliveras, Stefan Kempa, Sebastian Bachmann, Thomas J. Jentsch
Summary: The study found that all five VRAC subunits are expressed in the kidney with distinct localizations. LRRC8C is mainly found in vascular endothelial cells, LRRC8E is specific to intercalated cells, while LRRC8A, LRRC8B, and LRRC8D are prominent in the basolateral membranes of proximal tubules. Conditional deletion of LRRC8A in proximal tubules results in injury and symptoms.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Multidisciplinary Sciences
Shrikanth C. Basavarajappa, Angela Rose Liu, Anna Bruchez, Zhenlu Li, Vinicius G. Suzart, Zhonghua Liu, Yinghua Chen, Tsan Sam Xiao, Matthias Buck, Parameswaran Ramakrishnan
Summary: The modified trimeric RBD shows higher affinity binding to ACE2 and more effectively blocks CoV-2 infection compared to the monomeric RBD, indicating its potential as a first-line therapeutic method to control COVID-19.
Article
Immunology
Cheryl C. Collins, Peter Hahn, Zhaozhao Jiang, Katherine A. Fitzgerald, Tsan Sam Xiao, Ralph C. Budd
Summary: gd T cells are found at mucosal and epithelial barriers and tend to accumulate at sites of inflammation, infection, autoimmunity, and certain tumors. The ligands recognized by the gd T cell receptor (TCR) and the regulation of their expression are not fully understood. In this study, a soluble human TCR-gd tetramer was developed and shown to bind to monocytes activated by Borrelia burgdorferi, the causative agent of Lyme arthritis. Ligand expression on monocytes was found to be induced by Toll-like receptor agonists and dependent on NF-kB activation, caspase activation of the inflammasome, active metabolism, mitochondrial reactive oxygen species, and gasdermin-D activation. The ligand was expressed by a subset of metabolically active CD14+CD16+ monocytes and colocalized with mitochondria. These findings suggest that the synovial gd T cell ligand is a self-antigen whose expression is increased under inflammatory conditions and mitochondrial stress.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yamu Li, Zhonghua Liu, Yiqing Zhao, Jie Yang, Tsan Sam Xiao, Ronald A. Conlon, Zhenghe Wang
Summary: This study reveals that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers. ERBB3 modulates IFN-g-induced PD-L1 expression through the IRS1-PI3K-PDK1-RSK-CREB signaling axis. Additionally, ERBB3 mutations could serve as predictive biomarkers for tumors amenable to immune checkpoint therapy.
Article
Cell Biology
Jing Ze Wu, Mariia Zeziulia, Whijin Kwon, Thomas J. Jentsch, Sergio Grinstein, Spencer A. Freeman
JOURNAL OF CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sheng-yuan Zhang, Qiu-ping Xu, Li-na Shi, Shih-wen Li, Wei-hong Wang, Qing-qing Wang, Liao-xun Lu, Hui Xiao, Jun-hong Wang, Feng-ying Li, Yin-ming Liang, Si-tang Gong, Hao-ran Peng, Zheng Zhang, Hong Tang
Summary: T lymphopenia, commonly seen in the early phase of sepsis, is associated with increased morbidity and mortality. We have discovered that CD4(+) T cells interact with macrophages through MHC II to inhibit TLR pro-inflammatory signaling, thereby regulating excessive inflammation. This finding may contribute to the development of preventive treatments for sepsis.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Medicine, Research & Experimental
Anja Pfau, Karen I. Lopez-Cayuqueo, Nora Scherer, Matthias Wuttke, Annekatrin Wernstedt, Daniela Gonzalez Fassrainer, Desiree E. C. Smith, Jiddeke M. van de Kamp, Katharina Ziegeler, Kai-Uwe Eckardt, Friedrich C. Luft, Peter S. Aronson, Anna Koettgen, Thomas J. Jentsch, Felix Knauf
Summary: Sulfate is important for various physiological processes in the human body. The transporter SLC26A1 plays a crucial role in sulfate reabsorption in the kidney. Through genetic analysis and functional experiments, it is confirmed that SLC26A1 is a sulfate transporter in humans. Rare SLC26A1 variants are associated with lower plasma sulfate levels at the population level.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Virology
Wenlin Ren, Yunkai Zhu, Jun Lan, Hedi Chen, Yuyan Wang, Hongyang Shi, Fei Feng, Da-Yuan Chen, Brianna Close, Xiaomin Zhao, Jianping Wu, Boxue Tian, Zhenghong Yuan, Dongming Zhou, Mohsan Saeed, Xinquan Wang, Rong Zhang, Qiang Ding
Summary: This study suggests that genetic variability in ACE2 may contribute to the variable clinical outcomes of COVID-19, and identifies an ACE2 SNP, D355N, that restricts the spike protein-ACE2 interaction and has the potential to protect against SARS-CoV-2 infection.
JOURNAL OF VIROLOGY
(2022)
Article
Urology & Nephrology
Karen Lopez-Cayuqueo, Rosa Planells-Cases, Matthias Pietzke, Anna Oliveras, Stefan Kempa, Sebastian Bachmann, Thomas J. Jentsch
Summary: This study found that VRAC/LRRC8 channels play an important role in the kidney, particularly in the function and integrity of proximal tubules. LRRC8 channels may be crucial for the basolateral exit of many organic compounds.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)