Article
Developmental Biology
Farah Saad, David R. Hipfner
Summary: The Hedgehog (Hh) pathway is regulated by G protein-coupled receptors (GPCRs) in Drosophila, with Mthl5 identified as a modulator of this pathway. This suggests potential crosstalk between GPCRs and the Hh pathway in mammals as well.
Article
Genetics & Heredity
Sirinart Techa, Wilawan Thongda, Phimsucha Bunphimpapha, Wanwipa Ittarat, Manon Boonbangyang, Alisa Wilantho, Chumpol Ngamphiw, Boonyarath Pratoomchat, Prachumporn Nounurai, Sanit Piyapattanakorn
Summary: Recent studies have shown that genes in the GPCR superfamily play an important role in molting in crustaceans. In this study, four forms of GPCRs were identified in the mud crab, Scylla olivacea. These forms have common features in their structure and differ in the extracellular region. Two of these forms were found to be upregulated during molting, correlating with the demand for cholesterol used in hormone synthesis.
Article
Biochemistry & Molecular Biology
Enric Lizano, Jozie L. Hayes, Francis S. Willard
Summary: GPCRs are the largest family of membrane-spanning receptors in metazoans, mediating various biological processes. Adhesion GPCRs, which are activated by an intrinsic proteolytic mechanism, are a relatively understudied class of GPCRs. Our novel enterokinase-activated tethered ligand system for ADGRG6(GPR126) provides a robust and specific tool for investigating the biological function of ADGRs and identifying ligands that engage these receptors.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Clinical Neurology
Serena Galosi, Luca Pollini, Maria Novelli, Katerina Bernardi, Martina Di Rocco, Simone Martinelli, Vincenzo Leuzzi
Summary: In recent years, there has been an increasing number of genetic diseases associated with epilepsy and movement disorders. This study focuses on genetic disorders affecting the G-protein-coupled receptor-cAMP signaling pathway, which result in distinctive clinical phenotypes including movement disorders and epilepsy. Understanding these rare disorders can have important implications for diagnostic suspicion and early detection, as well as for developing targeted treatments.
FRONTIERS IN NEUROLOGY
(2022)
Article
Immunology
Shaswati Chaki, Ibrahim Alkanfari, Saptarshi Roy, Aetas Amponnawarat, Yvonne Hui, Carole A. Oskeritzian, Hydar Ali
Summary: The calcium release-activated calcium channels (CRAC/Orai) contribute to the activation of mast cells (MCs) mediated by MRGPRX2/B2, and their inhibition may provide a novel approach for modulating SP-induced MC/MRGPRX2-mediated disorders.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Kinjal Patel, Nicola J. Smith
Summary: Primary cilia are important for sensing environmental changes in mammalian cells through the Sonic Hedgehog pathway. GPR161 is a significant player in primary cilia and its unique features may affect receptor function and cAMP compartmentalisation. The recent potential pairing of GPR161 and spexin-1 requires further investigation before GPR161 is considered 'deorphanised'. The constitutive activity and unconventional regulation of GPR161 suggest that it may not require an endogenous ligand.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Reid H. J. Olsen, Justin G. English
Summary: Enzymatic and cellular signaling biosensors are powerful tools for understanding complex biological systems. G protein-coupled receptors (GPCRs) are extensively studied using biosensors, which have expanded our knowledge of this important class of proteins. Transducer biosensors that measure receptor coupling and selectivity, with a focus on receptor association and activation of heterotrimeric signaling complexes, are of particular importance.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Cell Biology
Haoran Jiang, Daniella Galtes, Jialu Wang, Howard A. Rockman
Summary: This review explores the signaling pathways, dynamic structures, and physiological relevance of the three most important GPCR signaling effectors in the cardiovascular system: heterotrimeric G proteins, GPCR kinases (GRKs), and 8-arrestins. It summarizes their prominent roles in GPCR pharmacology before transitioning into less well-explored areas. The application of new technologies has contributed to an increasing understanding of GPCR structure and downstream effectors.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Li-Hua Zhao, Jingyu Lin, Su-Yu Ji, X. Edward Zhou, Chunyou Mao, Dan-Dan Shen, Xinheng He, Peng Xiao, Jinpeng Sun, Karsten Melcher, Yan Zhang, Xiao Yu, H. Eric Xu
Summary: This study presents the structures of CRF2R bound to UCN1 and coupled to G proteins G(11) and G(o), and compares them with the structure of CRF2R bound to G(s), uncovering the structural differences that determine the selective coupling of G protein subtypes by CRF2R.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Stephen P. H. Alexander, Arthur Christopoulos, Anthony P. Davenport, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Adam J. Pawson, Christopher Southan, Jamie A. Davies, Maria Pia Abbracchio, Wayne Alexander, Khaled Al-hosaini, Magnus Baeck, Nicholas M. Barnes, Ross Bathgate, Jean-Martin Beaulieu, Kenneth E. Bernstein, Bernhard Bettler, Nigel J. M. Birdsall, Victoria Blaho, Francois Boulay, Corinne Bousquet, Hans Braeuner-Osborne, Geoffrey Burnstock, Girolamo Calo, Justo P. Castano, KevinJ Catt, Stefania Ceruti, Paul Chazot, Nan Chiang, Bice Chini, Jerold Chun, Antonia Cianciulli, Olivier Civelli, Lucie H. Clapp, Rejean Couture, Zsolt Csaba, Claes Dahlgren, Gordon Dent, Khuraijam Dhanachandra Singh, Steven D. Douglas, Pascal Dournaud, Satoru Eguchi, Emanuel Escher, Edward J. Filardo, Tung Fong, Marta Fumagalli, Raul R. Gainetdinov, Marc de Gasparo, Craig Gerard, Marvin Gershengorn, Fernand Gobeil, Theodore L. Goodfriend, Cyril Goudet, Karen J. Gregory, Andrew L. Gundlach, Joerg Hamann, Julien Hanson, Richard L. Hauger, Debbie L. Hay, Akos Heinemann, Morley D. Hollenberg, Nicholas D. Holliday, Mastgugu Horiuchi, Daniel Hoyer, Laszlo Hunyady, Ahsan Husain, Adriaan P. IJzerman, Tadashi Inagami, Kenneth A. Jacobson, Robert T. Jensen, Ralf Jockers, Deepa Jonnalagadda, Sadashiva Karnik, Klemens Kaupmann, Jacqueline Kemp, Charles Kennedy, Yasuyuki Kihara, Takio Kitazawa, Pawel Kozielewicz, Hans-Juergen Kreienkamp, Jyrki P. Kukkonen, Tobias Langenhan, Katie Leach, Davide Lecca, John D. Lee, Susan E. Leeman, Jerome Leprince, Xaria X. Li, Tom Lloyd Williams, Stephen J. Lolait, Amelie Lupp, Robyn Macrae, Janet Maguire, Jean Mazella, Craig A. McArdle, Shlomo Melmed, Martin C. Michel, Laurence J. Miller, Vincenzo Mitolo, Bernard Mouillac, Christa E. Mueller, Philip Murphy, Jean-Louis Nahon, Tony Ngo, Xavier Norel, Duuamene Nyimanu, Anne-Marie Ocarroll, Stefan Offermanns, Maria Antonietta Panaro, Marc Parmentier, Roger G. Pertwee, Jean-Philippe Pin, Eric R. Prossnitz, Mark Quinn, Rithwik Ramachandran, Manisha Ray, Rainer K. Reinscheid, Philippe Rondard, G. Enrico Rovati, Chiara Ruzza, Gareth J. Sanger, Torsten Schoeneberg, Gunnar Schulte, Stefan Schulz, Deborah L. Segaloff, Charles N. Serhan, Leigh A. Stoddart, Yukihiko Sugimoto, Roger Summers, Valerie P. Tan, David Thal, Walter (Wally) Thomas, PieterB M. W. M. Timmermans, Kalyan Tirupula, Giovanni Tulipano, Hamiyet Unal, Thomas Unger, Celine Valant, Patrick Vanderheyden, David Vaudry, Hubert Vaudry, Jean-Pierre Vilardaga, Christopher S. Walker, Ji Ming Wang, Donald T. Ward, Hans-Juergen Wester, Gary B. Willars, Trent M. Woodruff, Chengcan Yao, Richard D. Ye
Summary: The Concise Guide to PHARMACOLOGY 2021/22 presents concise overviews of nearly 1900 human drug targets with an emphasis on selective pharmacology, along with links to a more detailed knowledgebase. It serves as a permanent, citable record for researchers, providing useful information in the field of pharmacology.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Estefania Moreno, Nil Casajuana-Martin, Michael Coyle, Baruc Campos Campos, Ewa Galaj, Claudia Llinas del Torrent, Arta Seyedian, William Rea, Ning-Sheng Cai, Alessandro Bonifazi, Benjamin Floran, Zheng-Xiong Xi, Xavier Guitart, Vicent Casado, Amy H. Newman, Christopher Bishop, Leonardo Pardo, Sergi Ferre
Summary: This study provides evidence that heteromerization of G protein-coupled receptors (GPCRs), specifically dopamine D1 and D3 receptors, can influence the pharmacological properties of selective ligands. In vivo experiments support the involvement of D1R-D3R heteromers in the development of L-DOPA-induced dyskinesia in Parkinson's disease, suggesting the potential of targeting GPCR heteromers for drug development.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Na Wu, Agnieszka M. Olechwier, Cyrill Brunner, Patricia C. Edwards, Ching-Ju Tsai, Christopher G. Tate, Gebhard F. X. Schertler, Gisbert Schneider, Xavier Deupi, Renato Zenobi, Pikyee Ma
Summary: Developed high-sensitivity, high-throughput MALDI-MS method to study the interaction between GPCRs and signaling partners, focusing on GPCR-G protein complex formation. Studied over 70 ligand-GPCR-partner protein combinations to determine selectivity and binding affinities, demonstrating the potential for broad use in screening GPCR-targeting drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Juergen Einsiedel, Maximilian F. Schmidt, Harald Huebner, Peter Gmeiner
Summary: A broadly applicable synthesis method was developed for peptides incorporating mixed disulfides between cysteine and homocysteine and cysteamine. The method was successfully applied to pharmacologically relevant GPCR ligands and showed covalent binding to neurotensin receptor 1 in a radioligand depletion study.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Ilana B. Kotliar, Emily Lorenzen, Jochen M. Schwenk, Debbie L. Hay, Thomas P. Sakmar
Summary: G protein-coupled receptors (GPCRs) interact with a variety of membrane proteins, but the extent and mechanisms of these interactions are not well understood. RAMPs, a class of GPCR-interacting proteins, have been extensively studied. Recent research suggests that GPCR-RAMP interactions may be more widespread than previously thought. This review summarizes the latest techniques for discovering GPCR-RAMP interactions and their functional consequences, and discusses future research prospects.
PHARMACOLOGICAL REVIEWS
(2023)
Review
Cell Biology
Aiqi Yin, Xiaonian Guan, Jian Zhang, Jianmin Niu
Summary: Preeclampsia is a clinical syndrome characterized by hypertension and proteinuria, and its etiology and pathogenesis are not fully understood. Obesity, immunological diseases, and endocrine metabolic diseases are high-risk factors for preeclampsia. The pathogenesis of preeclampsia involves poor placentation, uteroplacental malperfusion, oxidative stress, immune tolerance dysregulation, vascular inflammation, and endothelial cell dysfunction. The placenta is considered a core factor in the pathogenesis of preeclampsia. G protein-coupled receptors, specifically the secretin/adhesion (Class B) receptors, have potential roles as drug targets in placental development and preeclampsia treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)