Article
Multidisciplinary Sciences
Takefumi Kimura, Sai P. Pydi, Lei Wang, Dhanush Haspula, Yinghong Cui, Huiyan Lu, Gabriele M. Koenig, Evi Kostenis, Gregory R. Steinberg, Oksana Gavrilova, Juergen Wess
Summary: This study found that by activating adipocyte G(q) signaling, the increased lipolysis in obese individuals can be prevented, leading to improved glucose and lipid homeostasis. This has important implications for the development of novel anti-diabetic drugs based on GPCR.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Ahmed Wagdi, Daniela Malan, Udhayabhaskar Sathyanarayanan, Janosch S. Beauchamp, Markus Vogt, David Zipf, Thomas Beiert, Berivan Mansuroglu, Vanessa Dusend, Mark Meininghaus, Linn Schneider, Bernd Kalthof, J. Simon Wiegert, Gabriele M. Konig, Evi Kostenis, Robert Patejdl, Philipp Sasse, Tobias Bruegmann
Summary: This study presents a new optogenetic tool, human Neuropsin (hOPN5), which allows for specific and repetitive manipulation of G(q) signaling with high spatio-temporal resolution. The researchers characterized the properties and G protein specificity of hOPN5 using UV light-induced IP3 generation, Ca2+ transients, and inhibition of G(IRK) channel activity. They demonstrated that light could increase the beating rate of adult hearts and induce contractions in the small intestine, both of which were dependent on G(q) signaling. Additionally, the authors showed that all-optical high-throughput screening using hOPN5 was more specific and sensitive compared to conventional pharmacological screening.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Evgenii Gerasimov, Ilya Bezprozvanny, Olga L. L. Vlasova
Summary: This study investigated the effects of optogenetic activation of astrocytes in a mouse model of Alzheimer's disease. The results showed that chronic activation of astrocytes improved spine density, promoted the survival of mushroom spines, and enhanced performance in cognitive behavioral tests. Furthermore, the chronic optogenetic stimulation of astrocytes upregulated the expression of the EAAT-2 glutamate uptake transporter. These findings suggest that persistent activation of astrocytes may have therapeutic potential for Alzheimer's disease and other neurodegenerative disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Diana Zindel, Patrick Mensat, Claire Vol, Zeinab Homayed, Fabienne Charrier-Savournin, Eric Trinquet, Jean-Louis Baneres, Jean-Philippe Pin, Julie Pannequin, Thomas Roux, Elodie Dupuis, Laurent Prezeau
Summary: The Hippo pathway is a key kinase cascade that regulates tissue homeostasis, cellular differentiation, and organ size. By studying the ghrelin receptor, a GPCR that activates Gq exclusively, researchers have shown that GPCRs can finely modulate YAP activity through the Gq pathway.
Article
Biochemistry & Molecular Biology
Yu Qian, Zhengxiong Ma, Chunhong Liu, Xinzhi Li, Xinyan Zhu, Na Wang, Zhenmei Xu, Ruixue Xia, Jiale Liang, Yaning Duan, Han Yin, Yangjie Xiong, Anqi Zhang, Changyou Guo, Zheng Chen, Zhiwei Huang, Yuanzheng He
Summary: In this study, cryoelectron microscopy (cryo-EM) structures of ADGRL3 in complex with G(q), G(s), G(i), and G(12) were determined, revealing the unique ligand-engaging mode and activation conformation of aGPCRs. The study also provides insights into the structural information of GPCR/G12 coupling and the key determinant of G-protein coupling.
Article
Multidisciplinary Sciences
Yong-Seok Kim, Jun-Hee Yeon, Woori Ko, Byung-Chang Suh
Summary: In this study, the authors developed a FRET tool to investigate the conformational changes of the hM3R receptor during the activation-deactivation cycle of G proteins. They found that G protein activation induces a two-step change in the hM3R structure, and the separated G alpha(q)-GTP forms a stable complex with the activated receptor. This study provides real-time insights into the conformational dynamics of the hM3R receptor during the downstream G(q) protein cycle.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Hanako Hagio, Wataru Koyama, Shiori Hosaka, Aysenur Deniz Song, Janchiv Narantsatsral, Koji Matsuda, Tomohiro Sugihara, Takashi Shimizu, Mitsumasa Koyanagi, Akihisa Terakita, Masahiko Hibi, Suresh Jesuthasan
Summary: We examined the functionality of animal G-protein-coupled bistable rhodopsins in zebrafish by controlling them into active and inactive states using light application. The Gq-coupled spider Rh1 expressed in hindbrain reticulospinal V2a neurons increased intracellular Ca2+ levels and induced swimming behavior upon light stimulation. The Gi/o-coupled mosquito Opn3, pufferfish TMT opsin, or lamprey parapinopsin expressed in cardiomyocytes caused cardiac arrest, which could be suppressed by pertussis toxin or barium treatment, indicating the regulation of cardiac function by Gi/o-dependent inward-rectifier K+ channels. These rhodopsins are valuable tools for optogenetic control of GPCR-mediated signaling in zebrafish neurons and cardiomyocytes.
Article
Medicine, Research & Experimental
Liu Liu, Diptadip Dattaroy, Katherine F. Simpson, Luiz F. Barella, Yinghong Cui, Yan Xiong, Jian Jin, Gabriele M. Konig, Evi Kostenis, Jefferey C. Roman, Klaus H. Kaestner, Nicolai M. Doliba, Jurgen Wess
Summary: This study demonstrates that by activating G(q) signaling pathway, glucagon can be released to improve insulin secretion and glucose tolerance. Chronic activation of this pathway also benefits glucose metabolism in obese mice. Additionally, the activation of V1bR receptor stimulates glucagon release, highlighting its role in regulating glucagon secretion under hypoglycemic conditions.
Article
Biology
Anja Floeser, Katharina Becker, Evi Kostenis, Gabriele Konig, Cornelius Krasel, Peter Kolb, Moritz Buenemann
Summary: The study compared the efficacy of seven agonists in inducing interactions with M3 muscarinic acetylcholine receptors, finding substantial differences in the induction of M3R-arrestin3 versus M3R-GRK2 interaction.
Article
Medicine, General & Internal
Helma Freitag, Marvin Szklarski, Sebastian Lorenz, Franziska Sotzny, Sandra Bauer, Aurelie Philippe, Claudia Kedor, Patricia Grabowski, Tanja Lange, Gabriela Riemekasten, Harald Heidecke, Carmen Scheibenbogen
Summary: The study found that levels of specific AAB were significantly correlated with fatigue and muscle pain symptoms in patients with infection-triggered ME/CFS, while patients with non-infection-triggered ME/CFS showed fewer correlations. This suggests a potential role of AAB or respective receptor pathways in the pathomechanism of the disease.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Linda K. Myers, Ying-Xin Ouyang, Jay R. Patel, Herman H. Odens, Virginia Woo-Rasberry, Jeoungeun Park, Ae-Kyung Yi, Edward F. Rosloniec, David D. Brand, John M. Stuart, Andrew H. Kang
Summary: Cit-CI acts as an antagonist of LAIR-1 signaling, and the severity of autoimmune arthritis can be effectively altered by targeting T cells with citrullinated collagen. Citrullination of proteins plays an important role in protein function and immune responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Krzysztof Jozwiak, Anita Plazinska
Summary: Studies on different receptors belonging to class A of GPCRs reveal specific molecular mechanisms behind ligand directed signaling, including the role of important residues, the impact of ligand structural features on signaling, and the key interactions between ligands and receptors.
Article
Pharmacology & Pharmacy
Stephan Hasse, Anne-Claire Duchez, Paul Fortin, Eric Boilard, Sylvain G. Bourgoin
Summary: Studies show that red blood cells play a crucial role in vascular homeostasis and lysophosphatidic acid can induce the production of extracellular vesicles in red blood cells. Different LPA species have varying effects on red blood cells through targeting LPA2 and/or LPA3 receptors, with LPA 16:0, 18:0, and 18:1 inducing phosphatidylserine exposure and release of vesicles.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yang Zhao, Stephan Hasse, Sylvain G. Bourgoin
Summary: PLA1A is an enzyme expressed in various human tissues and cells, involved in regulating immune cell maturation and function through hydrolyzing PS or 1-acyl-lysoPS. High levels of PLA1A expression are associated with autoimmune disorders, cancers, and cardiometabolic disorders. Additionally, PLA1A plays a role in hepatitis C virus assembly and antivirus innate immune response.
PROGRESS IN LIPID RESEARCH
(2021)
Article
Cell Biology
Ze-Yan Yu, Hutao Gong, Jianxin Wu, Yun Dai, Scott H. Kesteven, Diane Fatkin, Boris Martinac, Robert M. Graham, Michael P. Feneley
Summary: Activation of Gq-coupled receptors and calcineurin are necessary for neurohumorally mediated left ventricular hypertrophy (LVH), while LVH induced by mechanical pressure overload (TAC) is associated with activation of the CaMKII-HDAC4-MEF2 pathway.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Rheumatology
Guihua Fan, Fan Dai, Shiju Chen, Yuechi Sun, Hongyan Qian, Guomei Yang, Yuan Liu, Guixiu Shi
Summary: Neurological involvement is common in patients with primary Sjogren's syndrome (pSS) and needs careful evaluation. Patients with pSS with high anti-SSA titers and low anti-SSB presence may have a relatively high risk of developing neurological involvement. Future studies should focus on identifying biomarkers for early diagnosis of neurological involvement in patients with pSS.
JCR-JOURNAL OF CLINICAL RHEUMATOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Yesi Shi, Fengfei Xie, Peishi Rao, Hongyan Qian, Rongjuan Chen, Hu Chen, Dengfeng Li, Dan Mu, Lili Zhang, Peng Lv, Guixiu Shi, Li Zheng, Gang Liu
JOURNAL OF CONTROLLED RELEASE
(2020)
Article
Immunology
Bin Wang, Shiju Chen, Qing Zheng, Yuan Liu, Guixiu Shi
JOURNAL OF IMMUNOLOGY RESEARCH
(2020)
Article
Endocrinology & Metabolism
Yaogui Ning, Guomei Yang, Yangchun Chen, Xue Zhao, Hongyan Qian, Yuan Liu, Shiju Chen, Guixiu Shi
FRONTIERS IN ENDOCRINOLOGY
(2020)
Article
Rheumatology
Junhui Zhang, Yuan Liu, Guixiu Shi
Summary: This study identified 29 differentially expressed circRNAs and constructed a regulatory network including 8 DECs, 4 miRNAs, and 13 mRNAs, providing novel insights into the role circRNAs play in the regulation network of SLE. Further verification through experiments and clinical studies is needed.
CLINICAL RHEUMATOLOGY
(2021)
Article
Rheumatology
Min Li, Gong Cheng, Zongyi Wang, Wen Liu, Yuebo Jin, Bo Huang, Yifan Wang, Jinfeng Qu, Guixiu Shi, Yin Su, Jing He, Zhanguo Li
Letter
Rheumatology
Bin Wang, Shiju Chen, Jingxiu Xuan, Yan Li, Qing Zheng, Xinwei Zhang, Yuan Liu, Guixiu Shi
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Immunology
Bin Wang, Shiju Chen, Qing Zheng, Yan Li, Xinwei Zhang, Jingxiu Xuan, Yuan Liu, Guixiu Shi
Summary: Challenges and unmet needs exist in the early diagnosis and management of Sjogren's syndrome, partly due to lack of understanding of the early stages of the disease. Findings suggest a redefined course of SjS with 4 stages, emphasizing the importance of studying pathological processes and identifying useful biomarkers for early diagnosis and treatment.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Rheumatology
Qing Zheng, Wen Liu, Yu Huang, Zhenyu Gao, Yuanhui Wu, Xiaohong Wang, Meimei Cai, Yan He, Shiju Chen, Bin Wang, Lingyu Liu, Shuqiang Chen, Hongjie Huang, Ling Zheng, Rihui Kang, Xiaohong Zeng, Jing Chen, Huaning Chen, Junmin Chen, Zhibin Li, Guixiu Shi
Summary: This study examined the predictive model for flare in axSpA patients, finding significant associations between active sacroiliitis on MRI, anti-TNF-alpha treatment, and disease flares. The nomogram prediction model showed better performance in discriminating and calibrating in clinical practice.
RHEUMATOLOGY AND THERAPY
(2021)
Article
Immunology
Yichen Liang, Zhenhua Xian, Dehua Fu, Shuang Liu, Yang Yao, Yuebo Jin, Chun Gao, Long Shen, Guixiu Shi, Jing He
Summary: This study evaluated the potential of IL-14 alpha as a biomarker for dry eye in primary Sjogren's syndrome and its correlation with BAFF in different patient groups. The results indicated that IL-14 alpha and BAFF could serve as critical cytokine biomarkers for the stratification of dry eye in pSS, providing insights for non-invasive diagnosis methods.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Bin Wang, Shiju Chen, Yan Li, Jingxiu Xuan, Yuan Liu, Guixiu Shi
Summary: Primary Sjogren's syndrome (pSS) is an autoimmune exocrinopathy characterized by dryness symptoms, and targeted therapies for pSS still face challenges. Promising biologics like ianalumab and iscalimab need further evaluation in larger clinical trials for efficacy.
Article
Rheumatology
Yuan Liu, Shiju Chen, Guomei Yang, Bin Wang, Jinying Lan, Fan Dai, Peishi Rao, Puqi Wu, Hongyan Qian, Guixiu Shi
Summary: The study clarified the higher risk of developing CTDs, especially SLE, among ANA-positive primary ITP patients, supporting the idea that ANA-positive primary ITP is a distinct clinical entity.
LUPUS SCIENCE & MEDICINE
(2021)
Article
Immunology
Bin Wang, Shiju Chen, Hongyan Qian, Qing Zheng, Rongjuan Chen, Yuan Liu, Guixiu Shi
INTERNATIONAL IMMUNOPHARMACOLOGY
(2020)
Article
Pharmacology & Pharmacy
Hongyan Qian, Rongjuan Chen, Bin Wang, Xiaoqing Yuan, Shiju Chen, Yuan Liu, Guixiu Shi
FRONTIERS IN PHARMACOLOGY
(2020)
Article
Immunology
Jingxiu Xuan, Zhiqian Ji, Bin Wang, Xiaoli Zeng, Rongjuan Chen, Yan He, Peishi Rao, Puqi Wu, Guixiu Shi
FRONTIERS IN IMMUNOLOGY
(2020)
