Article
Medicine, General & Internal
Gerd Wallukat, Stephan Mattecka, Katrin Wenzel, Wieland Schroedl, Birgit Vogt, Patrizia Brunner, Ahmed Sheriff, Rudolf Kunze
Summary: This study found that C-reactive protein (CRP) affects intracellular calcium signaling and blood pressure. When CRP is combined with GPCR agonists in cardiomyocytes, it can interfere with the desensitization of GPCRs, regardless of the type of GPCR, but dependent on the concentration of CRP.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Xianmei Gou, Lin Qin, Di Wu, Jian Xie, Yanliu Lu, Qianru Zhang, Yuqi He
Summary: Bile acids are recognized as signaling molecules involved in metabolic syndrome, and Takeda G protein-coupled receptor 5 (TGR5) acts as a significant receptor for bile acids, which is associated with lipid homeostasis, glucose metabolism, and inflammation regulation. Recent preclinical studies suggest that TGR5 plays a crucial role in the generation and progression of metabolic syndrome, including type 2 diabetes mellitus, obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). This review discusses the role of TGR5 in metabolic syndrome, highlighting the underlying mechanisms and therapeutic targets.
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
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
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
Bui San Thai, Ling Yeong Chia, Anh T. N. Nguyen, Chengxue Qin, Rebecca H. Ritchie, Dana S. Hutchinson, Andrew Kompa, Paul J. White, Lauren T. May
Summary: Heart failure remains a significant cause of morbidity and mortality worldwide. Current treatment options have limitations, leading to many patients progressing to advanced stages. Exploration of novel therapeutics targeting G protein-coupled receptors (GPCRs) has shown promise, but efficacy and unwanted effects remain as challenges.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Mydirah Littlepage-Saunders, Michael J. Hochstein, Doris S. Chang, Kari A. Johnson
Summary: Dopamine transmission in the striatum is regulated by various G protein-coupled receptors (GPCRs) that bind neuromodulators, including dopamine itself. These GPCRs can modulate dopamine release by acting on different components of the dopaminergic circuitry and can have distinct effects on behavior and psychoactive drug actions. This review discusses the mechanisms by which GPCRs regulate dopaminergic transmission and their relevance to the effects of psychoactive drugs on physiology and behavior.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Damian Jacenik, Pawel Hikisz, Ellen J. Beswick, Jakub Fichna
Summary: Among the various adhesion G protein-coupled receptors, ADGRF5 stands out with its unique domains in the N-terminal tail that play a critical role in cell-cell and cell-matrix interactions, as well as cell adhesion. Although the biology of ADGRF5 is still not fully understood, accumulating evidence suggests its fundamental importance in both health and disease. Recent studies have highlighted its potential diagnostic value in osteoporosis and cancers, and ongoing research indicates its relevance to other diseases as well. This article provides a comprehensive overview of the current understanding of ADGRF5 in human disease physiology and pathophysiology, emphasizing its potential as a novel therapeutic target in various areas.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Raudah Lazim, Donghyuk Suh, Jai Woo Lee, Thi Ngoc Lan Vu, Sanghee Yoon, Sun Choi
Summary: The presence of GPCR dimers has sparked research into their importance in disease pathogenesis and drug design, uncovering new signaling pathways and potential therapeutic targets. The increasing influence of computational methods in research is providing new avenues for understanding the functions and interactions of GPCRs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Alastair C. Keen, Manuela Jorg, Michelle L. L. Halls
Summary: The ubiquitin-proteasome system is a major pathway for protein degradation in cells, and methods have been developed to exploit this system for targeted protein degradation. Targeted protein degraders have been useful tools in discovery research and are being developed as therapeutics. However, most targeted protein degrader technologies have been developed for cytosolic proteins, while examples for G protein-coupled receptor (GPCR) degradation are limited. This review discusses the strategies used for applying targeted protein degradation to GPCRs and explores alternative approaches used for degrading other integral membrane proteins.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Rina Pokhrel, Alexandra L. Morgan, Harley R. Robinson, Martin J. Stone, Simon R. Foster
Summary: G protein-coupled receptor (GPCR) activation triggers complex intracellular signalling networks, which have important implications for receptor biology and drug discovery. Phosphoproteomics has emerged as a powerful tool for investigating these networks and accelerating the discovery of new therapeutic targets.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shuai Luo, Peng Zhang, Wei Miao, Jie Xiong
Summary: This study provides the first comprehensive genome-wide identification of GPCRs in ciliates, identifying 492 GPCRs in 24 ciliates. GPCRs in ciliates can be assigned to four families, with most belonging to family A. Gene duplication events play a role in the expansion of the GPCR superfamily in ciliates. This study improves our understanding of the evolution and function of GPCRs in ciliates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Roberto Maggio, Irene Fasciani, Francesco Petragnano, Maria Francesca Coppolino, Marco Scarselli, Mario Rossi
Summary: Unstructured regions in functional proteins, specifically the i3 loop and C-terminus in G protein-coupled receptors (GPCRs), have been recognized as crucial elements in GPCR function and regulation. They play critical roles in allosterically regulating GPCR activation, as autoregulators in receptor coupling specificity, and in facilitating receptor stability and interactions with intracellular protein partners.
Article
Pharmacology & Pharmacy
Jyrki P. Kukkonen
Summary: Recent data indicates cooperative effects between identical orthosteric binding sites in a G-protein-coupled receptor dimer. A mathematical model was created to test this concept, showing that even a neutral receptor ligand can allosterically affect agonist binding through the orthosteric binding site.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yanan Tian, Chaohui Jiang, Yi Pan, Zhiqiang Guo, Weiwei Wang, Xumei Luo, Zheng Cao, Bing Zhang, Jingwen Yang, Ying Shi, Naiming Zhou, Xiaobai He
Summary: Two newly identified CCHamide receptors, BommoCCHaR-1 and -2, have been cloned and their specific endogenous ligands, CCHamide-1 and CCHamide-2, respectively, have been characterized. The receptors exhibit different signaling pathways upon activation, with BNGR-A14 eliciting increases in CRE-driven luciferase activity, intracellular Ca2+ mobilization, and ERK1/2 phosphorylation, while BNGR-A15 leads to intracellular accumulation of cAMP, Ca2+ mobilization, and ERK1/2 phosphorylation. Additionally, CCHamides are shown to require intrachain disulfide bonds for activation, and CCHamide-1 may regulate feeding behavior and growth through BNGR-A15, while CCHamide-2 plays a crucial role in multiple physiological processes.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sissy Bassani, Edward van Beelen, Mireille Rossel, Norine Voisin, Anna Morgan, Yoan Arribat, Nicolas Chatron, Jacqueline Chrast, Massimiliano Cocca, Benjamin Delprat, Flavio Faletra, Giuliana Giannuzzi, Nicolas Guex, Roxane Machavoine, Sylvain Pradervand, Jeroen J. Smits, Jiddeke M. van de Kamp, Alban Ziegler, Francesca Amati, Sandrine Marlin, Hannie Kremer, Heiko Locher, Tangui Maurice, Paolo Gasparini, Giorgia Girotto, Alexandre Reymond
Summary: Through exome sequencing and molecular assays, a novel autosomal dominant gene, USP48, has been identified as playing a crucial role in Non-Syndromic Hereditary Hearing Loss (NSHHL). Mutations in USP48 lead to impaired ability to hydrolyze tetra-ubiquitin. Immunohistology studies indicate expression of the encoded protein in the developing human inner ear, highlighting the role of USP48 in auditory function.
HUMAN MOLECULAR GENETICS
(2021)
Article
Genetics & Heredity
Mylene Tharreau, Aurore Garde, Sandrine Marlin, Godelieve Morel, Sylvain Ernest, Sophie Nambot, Yannis Duffourd, Ninon Ternoy, Christian Duvillard, Siddharth Banka, Christophe Philippe, Christel Thauvin-Robinet, Frederic Tran Mau-Them, Laurence Faivre
Summary: Loss-of-function variants in KMT2D can cause phenotypes different from KS1. Missense variants in KMT2D have been found in two families, providing further clinical and molecular understanding of this new entity. These variants may lead to milder and broader phenotypes, such as isolated CA and polydactyly.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Nancy Vegas, Zeynep Demir, Christopher T. Gordon, Sylvain Breton, Vanessa L. Romanelli Tavares, Hugo Moisset, Roseli Zechi-Ceide, Nancy M. Kokitsu-Nakata, Yasuhiro Kido, Sandrine Marlin, Souad Gherbi Halem, Ilse Meerschaut, Bert Callewaert, Brian Chung, Nicole Revencu, Daphne Lehalle, Florence Petit, Evan J. Propst, Blake C. Papsin, John H. Phillips, Linda Jakobsen, Pauline Le Tanno, Julien Thevenon, Julie McGaughran, Erica H. Gerkes, Chiara Leoni, Peter Kroisel, Tiong Y. Tan, Alex Henderson, Paulien Terhal, Lina Basel-Salmon, Adila Alkindy, Susan M. White, Maria R. Passos-Bueno, Veronique Pingault, Loic De Pontual, Jeanne Amiel
Summary: Auriculocondylar syndrome is a rare craniofacial disorder characterized by mandibular hypoplasia and an auricular defect. This research describes 14 new cases and reassesses 25 published cases, identifying additional features associated with the syndrome.
Review
Genetics & Heredity
Veronique Pingault, Lisa Zerad, William Bertani-Torres, Nadege Bondurand
Summary: SOX10, a member of the SOX protein family, plays a crucial role in cell specification and differentiation. Mutations in SOX10 can lead to various genetic disorders affecting neural crest derivatives and extraneural tissues, impacting development and health. Further research and understanding of these mutations can improve diagnosis and medical care for affected individuals.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Lucie Tosca, Loic Drevillon, Aurelie Mouka, Laure Lecerf, Audrey Briand, Valerie Ortonne, Virginie Benoit, Sophie Brisset, Lionel Van Maldergem, Quitterie Laudouar, Solveig Heide, Michel Goossens, Irina Giurgea, Gerard Tachdjian, Corinne Metay
Summary: Terminal deletions of chromosome 7 are often associated with holoprosencephaly, while interstitial deletions of CNTNAP2 may contribute to neurological abnormalities. Haploinsufficiency of specific genes may explain the clinical features observed in the patients, including hypotonia and long QT syndrome.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Daphne Lehalle, Ange-Line Bruel, Antonio Vitobello, Anne-Sophie Denomme-Pichon, Yannis Duffourd, Mirna Assoum, Jeanne Amiel, Genevieve Baujat, Bettina Bessieres, Stefania Bigoni, Lydie Burglen, Guillaume Captier, Rodolphe Dard, Patrick Edery, Fernanda Fortunato, David Genevieve, Alice Goldenberg, Laurent Guibaud, Delphine Heron, Muriel Holder-Espinasse, Damien Lederer, Fermina Lopez Grondona, Sarah Grotto, Sandrine Marlin, Gwenael Nadeau, Arnaud Picard, Massimiliano Rossi, Joelle Roume, Damien Sanlaville, Pascale Saugier-Veber, Stephane Triau, Maria Irene Valenzuela Palafoll, Clemence Vanlerberghe, Lionel Van Maldergem, Myriam Vezain, Catherine Vincent-Delorme, Einat Zivi, Julien Thevenon, Pierre Vabres, Christel Thauvin-Robinet, Patrick Callier, Laurence Faivre
Summary: This study aims to identify the molecular basis of Pai syndrome (PS) and reviewed cases of syndromic frontonasal polyps. The study confirmed that only a fraction of patients met the criteria for typical or atypical PS, while others had overlapping syndromes. Gene sequencing was inconclusive, suggesting the need for future research on affected tissues and multiomics studies.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Biochemistry & Molecular Biology
Maya Chopra, Richard Caswell, Giulia Barcia, Sophie Rondeau, Laurence Jonard, Patrick Nitchke, Daniel Amram, Marc-Lionel Bellaiche, Veronique Abadie, Marine Parodi, Francoise Denoyelle, Andrew Hattersley, Christine Bole, Stanislas Lyonnet, Sandrine Marlin
Summary: This article discusses how variants in different regions of the POLD1 gene can lead to different disease manifestations, with mutations in the CysB region potentially affecting iron-sulfur cluster binding without disrupting protein structure, playing a crucial role in regulating POLD1 activity.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
M. Mouille, M. Rio, S. Breton, M. L. Piketty, A. Afenjar, J. Amiel, Y. Capri, A. Goldenberg, C. Francannet, C. Michot, C. Mignot, L. Perrin, C. Quelin, J. Van Gils, G. Barcia, V Pingault, G. Maruani, E. Koumakis, V Cormier-Daire
Summary: This study systematically reviewed the skeletal manifestations of SATB2-associated syndrome and found that pathogenic variants in SATB2 are responsible for skeletal demineralization and osteoporosis. The study also discovered increased levels of bone formation markers, supporting the key role of SATB2 in osteoblast differentiation. Therefore, bone evaluation is recommended for children and adult patients with SATB2-associated syndrome.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Genetics & Heredity
Jeremy Dana, Guillaume Dorval, Christine Saint Martin, Kahina Belhous, Raphael Levy, Sandrine Marlin, Isabelle De Bie, Manon Mautret-Godefroy, Antonio Rausell, Marlene Rio, Elise Boucher-Brischoux, Tania Attie-Bitach, Nathalie Boddaert, Veronique Pingault
Summary: A retrospective cohort study was conducted to establish the genotype-phenotype correlation for CHD7-related CHARGE syndrome through unsupervised machine learning and clustering of 42 patients. Three clusters with different severities of phenotypes were identified. One patient with the most atypical phenotype and the most distal frameshift variant stood out in the third cluster. Two other patients with similar distal pathogenic variants showed tendencies towards mild and/or atypical phenotypes. These findings suggest that the milder phenotypes may result from the production of a protein retaining all functional domains, rather than escaping nonsense mediated RNA decay.
Article
Genetics & Heredity
Godelieve Morel, Sylvain Ernest, Margaux Serey-Gaut, Laurence Jonard, Abeke Ralyath Balogoun, Marine Parodi, Natalie Loundon, Sophie Achard, Sandrine Marlin
Summary: Cochleovestibular dysfunctions are rare conditions that are often misrecognized. A study on Tunisian siblings revealed a homozygous pathogenic variation in the RIPOR2 gene, leading to congenital bilateral profound hearing and vestibular dysfunctions. However, contrary to our findings, deaf mouse and zebrafish models with Ripor2 knockout had normal vestibular function.
Article
Biochemistry & Molecular Biology
Thomas Husson, Francois Lecoquierre, Gael Nicolas, Anne-Claire Richard, Alexandra Afenjar, Severine Audebert-Bellanger, Catherine Badens, Frederic Bilan, Varoona Bizaoui, Anne Boland, Marie-Noelle Bonnet-Dupeyron, Elise Brischoux-Boucher, Celine Bonnet, Marie Bournez, Odile Boute, Perrine Brunelle, Roseline Caumes, Perrine Charles, Nicolas Chassaing, Nicolas Chatron, Benjamin Cogne, Estelle Colin, Valerie Cormier-Daire, Rodolphe Dard, Benjamin Dauriat, Julian Delanne, Jean-Francois Deleuze, Florence Demurger, Anne-Sophie Denomme-Pichon, Christel Depienne, Anne Dieux, Christele Dubourg, Patrick Edery, Salima El Chehadeh, Laurence Faivre, Patricia Fergelot, Melanie Fradin, Aurore Garde, David Genevieve, Brigitte Gilbert-Dussardier, Cyril Goizet, Alice Goldenberg, Evan Gouy, Anne-Marie Guerrot, Anne Guimier, Ines Harzalla, Delphine Heron, Bertrand Isidor, Didier Lacombe, Xavier Le Guillou Horn, Boris Keren, Alma Kuechler, Elodie Lacaze, Alinoe Lavillaureix, Daphne Lehalle, Gaetan Lesca, James Lespinasse, Jonathan Levy, Stanislas Lyonnet, Godelieve Morel, Nolwenn Jean-Marcais, Sandrine Marlin, Luisa Marsili, Cyril Mignot, Sophie Nambot, Mathilde Nizon, Robert Olaso, Laurent Pasquier, Laurine Perrin, Florence Petit, Veronique Pingault, Amelie Piton, Fabienne Prieur, Audrey Putoux, Marc Planes, Sylvie Odent, Chloe Quelin, Sylvia Quemener-Redon, Melanie Rama, Marlene Rio, Massimiliano Rossi, Elise Schaefer, Sophie Rondeau, Pascale Saugier-Veber, Thomas Smol, Sabine Sigaudy, Renaud Touraine, Frederic Tran Mau-Them, Aurelien Trimouille, Julien Van Gils, Clemence Vanlerberghe, Valerie Vantalon, Gabriella Vera, Marie Vincent, Alban Ziegler, Olivier Guillin, Dominique Campion, Camille Charbonnier
Summary: Variants of uncertain significance (VUS) are a significant issue in the molecular diagnosis of rare diseases. Episignatures have been proposed as biomarkers to help classify VUS, but their prediction abilities vary. Some episignatures can be confidently used in a diagnostic setting, while others require larger validation sample sizes and further research.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Andrew K. Sobering, Laura M. Bryant, Dong Li, Julie McGaughran, Isabelle Maystadt, Stephanie Moortgat, John M. Graham, Arie van Haeringen, Claudia Ruivenkamp, Roos Cuperus, Julie Vogt, Jenny Morton, Charlotte Brasch-Andersen, Maria Steenhof, Lars Kjaersgaard Hansen, Elodie Adler, Stanislas Lyonnet, Veronique Pingault, Marlin Sandrine, Alban Ziegler, Tyhiesia Donald, Beverly Nelson, Brandon Holt, Oleksandra Petryna, Helen Firth, Kirsty McWalter, Jacob Zyskind, Aida Telegrafi, Jane Juusola, Richard Person, Michael J. Bamshad, Dawn Earl, Anne Chun-Hui Tsai, Katherine R. Yearwood, Elysa Marco, Catherine Nowak, Jessica Douglas, Hakon Hakonarson, Elizabeth J. Bhoj
Summary: Loss-of-function variants in PHF8 cause a rare intellectual disability syndrome characterized by developmental delay, craniofacial dysmorphology, and potentially orofacial clefting. This study expands the clinical phenotype of the syndrome and highlights the association with autism spectrum disorder and attention deficit hyperactivity disorder.
HUMAN GENETICS AND GENOMICS ADVANCES
(2022)
Article
Ophthalmology
Vasily M. Smirnov, Marco Nassisi, Saddek Mohand-Said, Crystel Bonnet, Anne Aubois, Celine Devisme, Thilissa Dib, Christina Zeitz, Natalie Loundon, Sandrine Marlin, Christine Petit, Bahram Bodaghi, Jose-Alain Sahel, Isabelle Audo
Summary: This study provides a detailed phenotypic description of rod-cone dystrophy associated with CLRN1 variants. The retinal phenotype includes visual acuity loss, visual field constriction, and retinal degeneration. Four pathogenic variants were identified in the study.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)