Article
Multidisciplinary Sciences
Katarina Nemec, Hannes Schihada, Gunnar Kleinau, Ulrike Zabel, Eugene O. Grushevskyi, Patrick Scheerer, Martin J. Lohse, Isabella Maiellaro
Summary: This study discovered that receptor-activity-modifying protein 2 (RAMP2) acts as a specific allosteric modulator of parathyroid hormone 1 receptor (PTH1R), shifting it to a preactivated state and affecting its downstream signaling. These findings provide a new avenue for modulating GPCR function and drug design.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Cell Biology
Yiwei Zhou, Jiyong Meng, Chanjuan Xu, Jianfeng Liu
Summary: G protein-coupled receptors (GPCRs) are a large membrane protein family involved in physiological and pathological activities, and various sensors have been developed to monitor conformational changes for high-throughput drug screening purposes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Hyunbin Kim, In-Yeop Baek, Jihye Seong
Summary: This review introduces genetically encoded fluorescent biosensors that can precisely monitor the real-time activation process of G protein-coupled receptors (GPCRs) in live cells. These sensors allow observation of the activation process of GPCRs, including the binding of extracellular ligands, conformational changes of GPCRs, recruitment of G proteins or beta-arrestin, internalization and trafficking of GPCRs, and downstream signaling events associated with GPCRs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xiaoyuan Ma, Meichun Gao, Henry F. Vischer, Rob Leurs
Summary: Conformational biosensors are useful tools in pharmacology to monitor the activation state of receptor proteins. The study presents a NanoBRET-based conformational biosensor for the histamine H3R receptor, allowing the detection of ligand efficacy on living cells. It also explores the biosensor's compatibility with photopharmacological ligands and its potential use in membrane preparations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Alan Le Mercier, Remy Bonnavion, Weijia Yu, Mohamad Wessam Alnouri, Sophie Ramas, Yang Zhang, Yannick Jaeger, Kenneth Anthony Roquid, Hyun-Woo Jeong, Kishor Kumar Sivaraj, Haaglim Cho, Xinyi Chen, Boris Strilic, Tjeerd Sijmonsma, Ralf Adams, Timm Schroeder, Michael A. Rieger, Stefan Offemanns
Summary: GPR182 is a new atypical chemokine receptor for CXCL10, CXCL12, and CXCL13, involved in regulating hematopoietic stem cell homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
C. Britton, M. C. Poznansky, P. Reeves
Summary: Historically, CXCR4 and CXCL12 are associated with the bone marrow niche and hematopoiesis, but CXCL12 has broad tissue expression. CXCR4 acts as a node impacting multiple cellular processes and disease, transitioning our perspective towards a polyfunctional signaling cascade.
Article
Biochemistry & Molecular Biology
Chayma El Khamlichi, Laetitia Cobret, Jean-Michel Arrang, Severine Morisset-Lopez
Summary: This study reveals the presence of spontaneous H3R dimers not only in transfected cells and rodent brains, but also in transfected cortical neurons, with the receptor able to adopt a range of allosteric conformations from inactive to active states.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Wissem Deraredj Nadim, Shalina Hassanaly, Helene Benedetti, Claudine Kieda, Catherine Grillon, Severine Morisset-Lopez
Summary: Research has shown that neurofibromin (Nf1) plays a significant role in melanogenesis by regulating the interaction between MC1R and melanocytes. The GAP activity of Nf1 is crucial for modulating intracellular signaling pathways involved in melanogenesis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Isra Al Zamel, Abdulrasheed Palakkott, Mohammed Akli Ayoub
Summary: The study found that AngII/AT1R does not promote PAR1 activation in the absence of thrombin, but the combination of thrombin and AngII results in their synergistic/allosteric action.
Article
Biochemistry & Molecular Biology
Shane C. Wright, Michel Bouvier
Summary: GPCRs continue to be a focus in drug discovery efforts due to their widespread expression and broad role in signal transduction. Despite over 800 GPCRs sharing a common architecture, unique differences govern ligand specificity and pathway selectivity. Recent biosensor development has reinforced the idea that biased signaling may become mainstream in drug discovery programs.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Review
Endocrinology & Metabolism
Gaoxian Chen, Detlef Obal
Summary: G protein-coupled receptors (GPCRs) are important transmembrane proteins involved in many physiological processes, and their targeted drug development has been widely promoted. However, research findings generated in immortal cell lines have limitations in correlating with clinical patients. Human induced pluripotent stem cells (hiPSCs) have the potential to overcome these limitations and expand GPCR research towards personalized medicine. This review discusses the challenges of detecting GPCRs in hiPSCs and summarizes existing and new labeling methods.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Eleonore W. E. Verweij, Reggie Bosma, Meichun Gao, Jelle van den Bor, Betty Al Araaj, Sabrina M. de Munnik, Xiaoyuan Ma, Rob Leurs, Henry F. Vischer
Summary: This study used bioluminescence resonance energy transfer (BRET)-based biosensors to measure the effects of different agonists on the H1R signaling pathway, and found that one of the agonists exhibited biased agonism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Immunology
Yukari Okamoto, Sojin Shikano
Summary: Chemokine receptors, particularly GPR15, are important in maintaining immune homeostasis and inflammation development by directing leukocyte migration to tissues. In recent years, the discovery of GPR15 as a colon-homing receptor for T cells and its ligand, C10orf99, has brought attention to their roles in various inflammatory and immune disorders. Understanding the molecular mechanisms that regulate GPR15 expression and functions will help in the development of targeted therapeutics for GPR15-related diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Elizabeth K. M. Johnstone, Mohammed Akli Ayoub, Rebecca J. Hertzman, Heng B. See, Rekhati S. Abhayawardana, Ruth M. Seeber, Kevin D. G. Pfleger
Summary: This study investigated the heteromerization of AT(2) and B-2 receptors in HEK293FT cells. The results demonstrated the functional interaction between these receptors and the differences in signaling, providing important evidence for studying GPCR pharmacology and signaling diversity.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Critical Care Medicine
Aida Meghraoui-Kheddar, Benjamin G. Chousterman, Noelline Guillou, Sierra M. Barone, Samuel Granjeaud, Helene Vallet, Aurelien Corneau, Karim Guessous, Charles de Roquetaillade, Alexandre Boissonnas, Jonathan M. Irish, Christophe Combadiere
Summary: This study aimed to identify early and specific immune signatures of sepsis severity, as well as to distinguish sepsis patients from those with noninfectious inflammatory syndrome. The results revealed two new subsets of neutrophils that are specific to sepsis and detectable through routine blood tests. This finding represents a key biological milestone that can lead to improvements in patient care.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Hematology
Yohann Garnier, Livia Claude, Patricia Hermand, Evely Sachou, Aurelie Claes, Kassandra Desplan, Bassel Chahim, Pierre-Marie Roger, Frederic Martino, Yves Colin, Caroline Le Van Kim, Veronique Baccini, Marc Romana
Summary: COVID-19 patients exhibit increased concentration and size of platelet-derived and endothelial cell-derived microparticles (MPs). These MPs trigger cell death and induce overexpression of adhesion molecules, leading to increased neutrophil adhesion and DNA trap release. Preincubation of these MPs can attenuate their cytotoxicity and induction. The study suggests that MPs play a key role in COVID-19 pathophysiology and annexin A5 may have therapeutic potential.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Alain Couvineau, Thierry Voisin, Pascal Nicole, Valerie Gratio, Anne Blais
Summary: Hypothalamic neuropeptides hypocretin/orexins, identified in 1998, not only regulate important functions in the central nervous system but also play a role in the peripheral nervous system. Their involvement in various physiological functions and diseases such as inflammation, metabolic syndrome, and cancers suggests that they could be potential therapeutic targets for multiple pathologies.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ingrid Langer, Jerome Jeandriens, Alain Couvineau, Swapnil Sanmukh, Dorota Latek
Summary: This article discusses the regulation of human immune system homeostasis by neuropeptides such as VIP and PACAP, as well as their interactions with receptors VPAC1, VPAC2, and PAC1. It also introduces the new concept of inhibiting VIP and PACAP receptors for the treatment of chronic inflammation and cancer, and the neuroprotective effects of activating these receptors.
Editorial Material
Immunology
Alexandre Boissonnas, Christophe Combadiere
Summary: The study shows that targeting the post-translational modification enzyme QPCTL can prevent the protection of CCL2 and CCL7, leading to the inactivation of their chemotactic function and limiting the recruitment of pro-tumoral macrophages.
Article
Cell Biology
Marie Laviron, Maxime Petit, Eleonore Weber-Delacroix, Alexis J. Combes, Arjun Rao Arkal, Sandrine Barthelemy, Tristan Courau, David A. Hume, Christophe Combadiere, Matthew F. Krummel, Alexandre Boissonnas
Summary: Tumor-associated macrophages (TAMs) adapt to the tumor microenvironment and exhibit different functions based on their localization in the stroma or neoplastic epithelium. Single-cell RNA sequencing and imaging techniques reveal that TAM subsets in different tissue territories and tumor lesions have distinct capacities to activate T cells and phagocytose tumor cells.
Article
Immunology
Amelie Guihot, Isabelle Plu, Cathia Soulie, Alice Rousseau, Cecilia Nakid-Cordero, Karim Dorgham, Christophe Parizot, Elena Litvinova, Julien Mayaux, Isabelle Malet, Paul Quentric, Behazine Combadiere, Christophe Combadiere, Olivia Bonduelle, Lucille Adam, Pierre Rosenbaum, Alexandra Beurton, Patrice Hemon, Patrice Debre, Vincent Vieillard, Brigitte Autran, Danielle Seilhean, Frederic Charlotte, Anne-Genevieve Marcelin, Guy Gorochov, Charles-Edouard Luyt
Summary: The immunopathological pulmonary mechanisms leading to Coronavirus Disease (COVID-19)-related death in adults are still poorly understood. This study found that despite strong antiviral CD4 T cell-specific responses migrating to the lung, disease severity still occurs, suggesting a potential pathogenic role for perivascular memory CD4 T cells in fatal COVID-19 pneumonia.
FRONTIERS IN IMMUNOLOGY
(2022)
Letter
Hematology
Marc Romana, Marjorie Leduc, Patricia Hermand, Johanna Bruce, Emilie-Fleur Gautier, Frederic Martino, Yohann Garnier, Veronique Baccini, Caroline Le Van Kim
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Letter
Hematology
Abdoul Karim Dembele, Patricia Hermand, Florence Missud, Emmanuelle Lesprit, Laurent Holvoet, Valentine Brousse, Ghislaine Ithier, Marie-Helene Odievre, Malika Benkerrou, Caroline Le Van Kim, Berengere Koehl
Article
Biochemistry & Molecular Biology
Ghislaine Guillemain, Jean-Jacques Lacapere, Lucie Khemtemourian
Summary: This article evaluates a new approach to preserve beta-cells by preventing the formation of hIAPP oligomers and fibrils, which can lead to beta-cell death. It also reviews the progress in understanding amyloidosis associated with neurodegenerative diseases and inflammation, and explores its potential implications in preserving pancreatic beta-cells.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Article
Biochemistry & Molecular Biology
Luminita Duma, Lucile Senicourt, Baptiste Rigaud, Vassilios Papadopoulos, Jean-Jacques Lacapere
Summary: Ligand binding to human TSPO has been widely used in clinical neuroimaging, but the interaction mechanism remains poorly understood. In this study, solid-state nuclear magnetic resonance (ssNMR) spectroscopy was used to investigate the apo form of recombinant mouse TSPO (mTSPO) reconstituted in lipids. The results provide insights into the molecular dynamics and conformational mobility of mTSPO in the absence of ligands. The findings suggest potential implications for ligand recognition and protein interactions.
Article
Pharmacology & Pharmacy
Karim Dorgham, Samuel Murail, Pierre Tuffery, Eric Savier, Jeronimo Bravo, Angelita Rebollo
Summary: This study investigated the binding of peptides to PP2A using docking and molecular dynamics, and characterized the secondary structure of the peptide using CD spectroscopy. The binding affinity between PP2A, Caspase 9, and the interfering peptide C9h was compared. The results support the use of peptides as potential therapeutic agents against cancer.
Article
Biochemistry & Molecular Biology
Sophie Combet, Francoise Bonnete, Stephanie Finet, Alexandre Pozza, Christelle Saade, Anne Martel, Alexandros Koutsioubas, Jean-Jacques Lacapere
Summary: This study deciphers the structure of mouse transfocator protein (TSPO) without ligand in different solvents, revealing that the structure of TSPO is more compact and stable in DPC compared to SDS.
Article
Hematology
Livia Claude, Frederic Martino, Patricia Hermand, Bassel Chahim, Pierre-Marie Roger, Marie de Bourayne, Yohann Garnier, Benoit Tressieres, Yves Colin, Caroline le van Kim, Marc Romana, Veronique Baccini
Summary: The severity of COVID-19 is associated with activation of caspase-1 and BTK, which are related to the procoagulant state of patients. In vitro experiments show that plasma from COVID-19 ICU patients can increase CD62P expression and caspase-1 activity in healthy platelets, which can be prevented by ibrutinib.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Biochemistry & Molecular Biology
Anne Blais, Annaig Lan, Francois Blachier, Robert Benamouzig, Pauline Jouet, Alain Couvineau
Summary: Inflammatory bowel diseases are chronic inflammation characterized by relapsing-remitting cycles. The study aimed to compare the efficacy of IFX and OxA in a mouse model of chemically induced colitis. OxA treatment demonstrated better efficiency in promoting mucosal healing and suppressing inflammatory factors compared to IFX, suggesting its potential as a promising new biotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)