Article
Cell Biology
Mohammed Akli Ayoub
Summary: Pathogens exploit the cellular and molecular pathways in host organisms through interactions with cell surface receptors like GPCRs and RTKs, interfering with their activation and downstream signaling pathways. This manipulation allows pathogens to redirect cell signaling and benefit from it. Understanding these interactions at the molecular level provides insights for developing new approaches to prevent and treat infections, such as pharmacologically targeting GPCRs and RTKs.
CELLULAR SIGNALLING
(2023)
Review
Cell Biology
Xueqing Tang, Jingwei Bian, Zijian Li
Summary: GPCR internalization can trigger signal activation, providing new insights and drug targets for receptor internalization. The process is tightly regulated, particularly through posttranslational modifications. This review summarizes different posttranslational modifications in GPCR internalization, analyzing their significance in internalization dynamics, routes, fates, and related diseases.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Review
Immunology
Yi Wang, Cheng-long Zhu, Peng Li, Qiang Liu, Hui-ru Li, Chang-meng Yu, Xiao-ming Deng, Jia-feng Wang
Summary: Sepsis is a life-threatening dysfunction caused by an uncontrolled host response to infection, leading to respiratory dysfunction and acute respiratory distress syndrome (ARDS). Neutrophils, the first line of defense against infection, play a major role in sepsis. However, studies have shown that despite high levels of chemokines at the site of infection, neutrophils cannot migrate properly and instead accumulate in the lungs, causing tissue damage and ARDS. Dysregulation of chemokine receptors, particularly G protein-coupled receptors (GPCRs), is implicated in impaired neutrophil migration. This review summarizes the signaling pathways and mechanisms by which GPCR dysfunction in sepsis leads to impaired neutrophil chemotaxis and proposes potential targets for intervention to improve neutrophil chemotaxis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Takuya Hara, Kazuko Saeki, Hiromi Jinnouchi, Saiko Kazuno, Yoshiki Miura, Takehiko Yokomizo
Summary: BLT2 is a GPCR mainly expressed in epithelial cells with lateral membrane localization, and its C-terminal domain plays a crucial role in maintaining epithelial barrier function. The interaction and transport mechanism of BLT2 to the plasma membrane, facilitated by LIN7C, contributes to its function in enhancing barrier function in epithelial cells.
Review
Medicine, Research & Experimental
Tian-Liang Ma, Yong Zhou, Chen-Yu Zhang, Zi-Ang Gao, Jia-Xi Duan
Summary: beta-arrestin2 is a scaffold protein that plays multiple roles in regulating GPCRs signal transduction, including mediating receptor internalization, kinase activation, and modulation of various signaling pathways, playing important roles in cellular functions and disease development.
Article
Biochemistry & Molecular Biology
Hugo Avila, Anh Truong, David Tyrpak, Shin-Jae Park, Siqi Lei, Yaocun Li, Curtis Okamoto, Sarah Hamm-Alvarez, J. Andrew MacKay
Summary: A novel tool based on ELP technology can modulate the structure of DNM2 quickly, precisely, and reversibly, forming distinct temperature-dependent structures with potential applications in dynamin-dependent biology.
Article
Pharmacology & Pharmacy
Vincent B. Luscombe, Luis Alberto Baena-Lopez, Carole J. R. Bataille, Angela J. Russell, David R. Greaves
Summary: In this study, heterologous cell lines with low GPR84 expression levels were developed to mimic the response of primary cells in a label-free cell electrical impedance sensing system. It was found that DL-175 exhibited a delayed impedance response, a delayed and suppressed activation of Akt, and impaired ability to internalise GPR84 from the plasma membrane compared to 6-OAU. These signalling differences were transient and occurred only at early time points in the low expressing cell lines, highlighting the importance of receptor number and kinetic readouts when evaluating signalling bias. These findings provide new insights into GPR84 signalling and the evaluation of newly developed agonists.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Cell Biology
Kristyna Pluhackova, Florian M. Wilhelm, Daniel J. Mueller
Summary: Studies have shown that GPCR receptor phosphorylation and local membrane composition cooperatively regulate the conformation and dynamics of the GPCR-arrestin complex, which in turn affects signal transduction and the binding specificity of arrestin. Therefore, a deeper understanding of the complex GPCR regulatory mechanisms is crucial for identifying novel pathways of pharmacological intervention.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Environmental Sciences
M. Sendra, P. Pereiro, M. P. Yeste, L. Mercado, A. Figueras, B. Novoa
Summary: This study used zebrafish as a model to investigate the uptake, trafficking, degradation, and genotoxicity of polystyrene nanoparticles at cellular and systemic levels. Results showed that nanoparticles mainly accumulated in the gut, leading to increased reactive oxygen species, decreased antioxidant gene expression, and induced migration of immune cells.
ENVIRONMENTAL POLLUTION
(2021)
Review
Pharmacology & Pharmacy
Austen B. Casey, Meng Cui, Raymond G. Booth, Clinton E. Canal
Summary: This review discusses the importance of blockade and activation of the serotonin 5-HT2A G protein-coupled receptor (5-HT2AR) in the treatment of psychiatric disorders, and the limitations and strengths of currently available selective 5-HT2AR antagonists.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Zhoubin Tan, Zhuowei Lei, Zisheng Yan, Xuetao Ji, Xiaoai Chang, Zhi Cai, Liang Lu, Yiwei Qi, Xiumei Yin, Xiao Han, Ting Lei
Summary: The study demonstrated that beta-arrestin2 signaling, rather than G protein pathways, mediates the inhibitory effects of D-2 receptor on pituitary tumor growth. The beta-arrestin2-biased agonist UNC9994 effectively suppressed pituitary tumor cell growth in vitro and in vivo by inducing intracellular reactive oxygen species. The complexity of responses of pituitary tumors to G protein signaling pathways suggests that D-2 receptor beta-arrestin2-biased ligands may offer improved therapeutic selectivity.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Preethi C. Karnam, Sergey A. Vishnivetskiy, Vsevolod V. Gurevich
Summary: Arrestins are a small family of proteins that bind G protein-coupled receptors (GPCRs) with high affinity to active phosphorylated GPCRs. They must have two sensors, which detect receptor-attached phosphates and the active receptor conformation independently, enabling transition into a high-affinity receptor-binding state. This transition involves a global conformational rearrangement that stabilizes the complex by bringing additional elements of the arrestin molecule in contact with a GPCR.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Analytical
Hyunbin Kim, Hae Nim Lee, Jaesik Choi, Jihye Seong
Summary: Internalized B2ARs can sustain their activity and cAMP production for several hours during the endosomal trafficking pathway. The temporal kinetics of B2AR activity can be well explained by an active-vesicle population model modified from the Ricker model.
ANALYTICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
J. D. Gross, D. W. Kim, Y. Zhou, D. Jansen, L. M. Slosky, N. B. Clark, C. R. Ray, X. Hu, N. Southall, A. Wang, X. Xu, E. Barnaeva, W. C. Wetsel, M. Ferrer, J. J. Marugan, M. G. Caron, L. S. Barak, K. Toth
Summary: This study discovered a novel GHSR(1a) agonist called N8279, which exhibits strong selectivity for G protein signaling, providing potential for treating disorders of disrupted dopamine homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Jissele A. Verdinez, Julien A. Sebag
Summary: This study identified two N-linked glycosylation sites within the N-terminal region of PKR2 and demonstrated that glycosylation at position 27 is crucial for its plasma membrane localization and signaling. Additionally, glycosylation at position 7 was found to decrease PKR2 signaling through G alpha(s) without affecting G alpha(q/)(11) signaling.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Maitri Y. Shah, Manuela Ferracin, Valentina Pileczki, Baoqing Chen, Roxana Redis, Linda Fabris, Xinna Zhang, Cristina Ivan, Masayoshi Shimizu, Cristian Rodriguez-Aguayo, Mihnea Dragomir, Katrien Van Roosbroeck, Maria Ines Almeida, Maria Ciccone, Daniela Nedelcu, Maria Angelica Cortez, Taghi Manshouri, Steliana Calin, Muharrem Muftuoglu, Pinaki P. Banerjee, Mustafa H. Badiwi, Jan Parker-Thornburg, Asha Multani, James William Welsh, Marcos Roberto Estecio, Hui Ling, Ciprian Tomuleasa, Delia Dima, Hui Yang, Hector Alvarez, M. James You, Milan Radovich, Elizabeth Shpall, Muller Fabbri, Katy Rezvani, Leonard Girnita, Ioana Berindan-Neagoe, Anirban Maitra, Srdan Verstovsek, Riccardo Fodde, Carlos Bueso-Ramos, Mihai Gagea, Guillermo Garcia Manero, George A. Calin
Article
Dermatology
Warangkana Lohcharoenkal, Kunal Das Mahapatra, Lorenzo Pasquali, Caitrin Crudden, Lara Kular, Yeliz Z. Akkaya Ulum, Lingyun Zhang, Ning Xu Landen, Leonard Girnita, Maja Jagodic, Mona Stahle, Eniko Sonkoly, Andor Pivarcsi
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2018)
Article
Oncology
Huiyuan Zheng, Ian W. H. Jarvis, Matteo Bottai, Kristian Dreij, Ulla Stenius
Article
Ophthalmology
Maria Fili, Eric Trocme, Louise Bergman, Thonnie Rose Ong See, Helder Andre, Katarina Bartuma, Leonard Girnita, Charlotta All-Eriksson, Stefan Seregard, Gustav Stalhammar
BRITISH JOURNAL OF OPHTHALMOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Muller Fabbri, Leonard Girnita, Gabriele Varani, George A. Calin
Editorial Material
Oncology
Min Jia, Trygve Andreassen, Lasse Jensen, Tone Frost Bathen, Indranil Sinha, Hui Gao, Chunyan Zhao, Lars-Arne Haldosen, Yihai Cao, Leonard Girnita, Siver Andreas Moestue, Karin Dahlman-Wright
Article
Oncology
Muyi Sun, Wei Zhou, Xingqun Qi, Guanhong Zhang, Leonard Girnita, Stefan Seregard, Hans E. Grossniklaus, Zeyi Yao, Xiaoguang Zhou, Gustav Stalhammar
Review
Cell Biology
Caitrin Crudden, Dawei Song, Sonia Cismas, Eric Trocme, Sylvya Pasca, George A. Calin, Ada Girnita, Leonard Girnita
Review
Cell Biology
Baoqing Chen, Junyan Li, Dongmei Chi, Iman Sahnoune, Steliana Calin, Leonard Girnita, George A. Calin
Editorial Material
Biochemistry & Molecular Biology
Caitrin Crudden, Leonard Girnita
Article
Toxicology
Rongrong Wu, Johan Hogberg, Mikael Adner, Patricia Ramos-Ramirez, Ulla Stenius, Huiyuan Zheng
PARTICLE AND FIBRE TOXICOLOGY
(2020)
Article
Gastroenterology & Hepatology
Baoqing Chen, Mihnea P. Dragomir, Linda Fabris, Recep Bayraktar, Erik Knutsen, Xu Liu, Changyan Tang, Yongfeng Li, Tadanobu Shimura, Tina Catela Ivkovic, Mireia Cruz De los Santos, Simone Anfossi, Masayoshi Shimizu, Maitri Y. Shah, Hui Ling, Peng Shen, Asha S. Multani, Barbara Pardini, Jared K. Burks, Hiroyuki Katayama, Lucas C. Reineke, Longfei Huo, Muddassir Syed, Shumei Song, Manuela Ferracin, Eiji Oki, Bastian Fromm, Cristina Ivan, Krithika Bhuvaneshwar, Yuriy Gusev, Koshi Mimori, David Menter, Subrata Sen, Takatoshi Matsuyama, Hiroyuki Uetake, Catalin Vasilescu, Scott Kopetz, Jan Parker-Thornburg, Ayumu Taguchi, Samir M. Hanash, Leonard Girnita, Ondrej Slaby, Ajay Goel, Gabriele Varani, Mihai Gagea, Chunlai Li, Jaffer A. Ajani, George A. Calin
Article
Biochemistry & Molecular Biology
Rongrong Wu, Johan Hogberg, Mikael Adner, Ulla Stenius, Huiyuan Zheng
Summary: ATX and LPA play important roles in lung fibrosis and cancer. Our study shows that CSi rapidly activates the ATX-LPA axis, leading to DNA damage in bronchial epithelial cells. ATX amplifies DNA damage via paracrine signaling, while CSi induces NLRP3 phosphorylation, mitochondrial depolarization, and DSBs.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Oncology
Caitrin Crudden, Takashi Shibano, Dawei Song, Mihnea P. Dragomir, Sonia Cismas, Julianna Serly, Daniela Nedelcu, Enrique Fuentes-Mattei, Andrei Tica, George A. Calin, Ada Girnita, Leonard Girnita
Summary: This study elucidates the molecular and biological roles of biased signaling downstream RTK, providing a novel approach to enhance the efficacy of anti-IGF1R-targeted therapy in cancer by targeting system bias. The findings suggest a promising strategy for the rational design or repurposing of therapeutics to selectively cross-target the IGF1R or other RTK.
Meeting Abstract
Oncology
T. Shibano, S. Cismas, C. Worrall, A. Girnita, L. Girnita
ANNALS OF ONCOLOGY
(2019)