A5049289749- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Chemokine receptors and signaling
- Protein Kinase Regulation and GTPase Signaling
- Congenital heart defects research
- Glycosylation and Glycoproteins Research
- Axon Guidance and Neuronal Signaling
- Chemical Synthesis and Analysis
- Force Microscopy Techniques and Applications
- Regulation of Appetite and Obesity
- Computational Drug Discovery Methods
- Immunotherapy and Immune Responses
- Heart Rate Variability and Autonomic Control
- Hippo pathway signaling and YAP/TAZ
- Congenital Heart Disease Studies
- Cardiovascular Function and Risk Factors
- Nicotinic Acetylcholine Receptors Study
- Monoclonal and Polyclonal Antibodies Research
- Adipose Tissue and Metabolism
- Neuroendocrine regulation and behavior
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Cardiomyopathy and Myosin Studies
- Cancer, Stress, Anesthesia, and Immune Response
- Neuroscience and Neuropharmacology Research
Inserm
2014-2025
Institut des Maladies Métaboliques et Cardiovasculaires
2014-2025
Université de Toulouse
2013-2025
Université Toulouse III - Paul Sabatier
1998-2023
Medical University of Vienna
2023
Washington University in St. Louis
2019
Centre Hospitalier Universitaire de Toulouse
2002-2017
Centre National de la Recherche Scientifique
2012-2017
Institut des Biomolécules Max Mousseron
2016
Université de Montpellier
2016
Abstract Despite the discovery of heterotrimeric αβγ G proteins ∼25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that plant-derived depsipeptide FR900359 (FR) is ideally suited to this task. Using multifaceted approach systematically characterize FR as inhibitor Gq/11/14 over all other mammalian Gα isoforms and elaborate its molecular mechanism action. We also use investigate whether inhibition Gq an effective...
We used a bioluminescence resonance energy transfer biosensor to screen for functional selective ligands of the human oxytocin (OT) receptor. demonstrated that OT promoted direct engagement and activation Gq all Gi/o subtypes at Other peptidic analogues, chosen because specific substitutions in key structural/functional residues, showed biased G protein subtypes. No ligand, except OT, activated GoA or GoB, and, with only one exception, peptides also Gi2 Gi3 but not Gi1, GoA, indicating...
Chemerin is a small chemotactic protein originally identified as the natural ligand of CMKLR1. More recently, two other receptors, GPR1 and CCRL2, have been reported to bind chemerin but their functional relevance remains poorly understood. In this study, we compared binding signaling properties three human receptors showed differences in mode receptor signaling. binds all with low nanomolar affinities. However, contribution C-terminus efficiency varies greatly amongst receptors. By using...
Hyperactivity of the renin–angiotensin–aldosterone system through angiotensin II (Ang II)/Ang type 1 receptor (AT1-R) axis constitutes a hallmark hypertension. Recent findings indicate that only subset AT1-R signaling pathways is cardiodeleterious, and their selective inhibition by biased ligands promotes therapeutic benefit. To date, synthetic have been described, whether natural peptides exhibit functional selectivity at remains unknown. In this study, we systematically determined efficacy...
Bioluminescence resonance energy transfer (BRET) and co-immunoprecipitation experiments revealed that heterotrimeric G proteins their effectors were found in stable complexes persisted during signal transduction. Adenylyl cyclase, Kir3.1 channel subunits several G-protein (Galpha(s), Galpha(i), Gbeta(1) Ggamma(2)) tagged with luciferase (RLuc) or GFP, the complementary fragments of YFP (specifically Gbeta(1)-YFP(1-158) Ggamma(2)-YFP(159-238), which heterodimerize to produce fluorescent...
Heptahelical receptors communicate extracellular information to the cytosolic compartment by binding an extensive variety of ligands. They do so through conformational changes that propagate intracellular signaling partners as receptor switches from a resting active conformation. This state has been classically considered unique and responsible for regulation all pathways controlled receptor. However, recent functional studies have challenged this notion called paradigm where would exist in...
Classically, the prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) receptor EP<sub>4</sub> has been classified as coupling to Gα<sub>s</sub> subunit, leading intracellular cAMP increases. However, signaling revealed be more complex and also involves pertussis toxin-sensitive Gα<sub>i</sub> proteins β-arrestin-mediated effects. There are now many examples of selective activation independent pathways by G protein-coupled (GPCR) ligands, a concept referred functional selectivity. Because most...
The G protein-coupled receptor GHS-R1a mediates ghrelin-induced growth hormone secretion, food intake, and reward-seeking behaviors. signals through Gq, Gi/o, G13, arrestin. Biasing signaling with specific ligands may lead to the development of more selective drugs treat obesity or addiction minimal side effects. To delineate ligand selectivity at signaling, we analyzed in detail efficacy a panel synthetic activating different pathways associated HEK293T cells. Besides β-arrestin2...
Significance G protein-coupled receptors (GPCRs), one of the largest cell surface receptor families, transmit their signals through coupling intracellular partners, such as proteins. Knowing how this occurs is essential, because it governs entire signaling process. To address open question, we used a purified GPCR model to which applied various state-of-the-art biochemical and biophysical approaches. By doing so, provide direct experimental evidence mechanism in conformational changes are...
In recent years, several studies have demonstrated that different ligands can distinct efficacy profiles toward various signaling pathways through a unique receptor. For example, β1-adrenergic compounds are inverse agonists the adenylyl cyclase (AC) display agonist activity for mitogen-activated protein kinase (MAPK) pathway. Such phenomenon, often termed functional selectivity, has now been clearly established many G protein-coupled receptors when considering output. However, possibility...
Purpose Autonomic dysfunction including sympathetic activation and vagal withdrawal has been reported in patients with chronic heart failure (CHF). We tested the hypotheses that high-intensity interval exercise (HIIE) CHF would enhance modulation thus decrease arrhythmic events. Methods Eighteen underwent a baseline assessment (CON) were then randomized to single session of HIIE an isocaloric moderate-intensity continuous (MICE). evaluated HR, HR variability parameters, events by 24-h Holter...
Significance G protein-coupled receptors (GPCRs) are one of the largest cell surface receptor family that transmit their signal through coupling to intracellular partners, such as proteins. Receptor oligomerization has been shown be pivotal in this signaling process. To address how can impact on a major physiological process, dopamine signaling, we used purified GPCR heteromer composed ghrelin and which applied variety state-of-the-art biochemical biophysical approaches. By doing so, provide...