A5064733011- Chemical Synthesis and Analysis
- Regulation of Appetite and Obesity
- Biochemical Analysis and Sensing Techniques
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Click Chemistry and Applications
- Adipose Tissue and Metabolism
- Peptidase Inhibition and Analysis
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Synthesis and Characterization of Heterocyclic Compounds
- Analytical Chemistry and Chromatography
- Pancreatic function and diabetes
- Synthetic Organic Chemistry Methods
- Chemical Synthesis and Reactions
- Asymmetric Synthesis and Catalysis
- Carbohydrate Chemistry and Synthesis
- Monoclonal and Polyclonal Antibodies Research
- Muscle Physiology and Disorders
- Advanced Synthetic Organic Chemistry
- Growth Hormone and Insulin-like Growth Factors
- Fluorine in Organic Chemistry
- Synthesis and Reactivity of Heterocycles
- Biochemical and Structural Characterization
- Biochemical effects in animals
- melanin and skin pigmentation
École Nationale Supérieure de Chimie de Montpellier
2016-2025
Institut des Biomolécules Max Mousseron
2016-2025
Université de Montpellier
2016-2025
Centre National de la Recherche Scientifique
2016-2025
Czech Academy of Sciences
2022
Czech Academy of Sciences, Institute of Physiology
2022
Charles University
2022
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2022
University of Chemistry and Technology, Prague
2022
Pharmac
2016
To maintain homeostasis, hypothalamic neurons in the arcuate nucleus must dynamically sense and integrate a multitude of peripheral signals. Blood-borne molecules therefore be able to circumvent tightly sealed vasculature blood-brain barrier rapidly access their target neurons. However, how information encoded by circulating appetite-modifying hormones is conveyed central remains largely unexplored. Using vivo multiphoton microscopy together with fluorescently labeled ligands, we demonstrate...
Despite its central role in signaling and the potential therapeutic applications of inverse agonists, molecular mechanisms underlying G protein-coupled receptor (GPCR) constitutive activity remain largely to be explored. In this context, ghrelin GHS-R1a is a peculiar sense that it displays strikingly high, physiologically relevant, activity. To identify responsible for high activity, we have reconstituted purified monomer lipid disc. Using system, show isolated per se activates Gq absence...
The ghrelin receptor or growth hormone secretagogue (GHSR) is a G-protein-coupled that controls and insulin secretion, food intake, reward-seeking behaviors. Liver-expressed antimicrobial peptide 2 (LEAP2) was recently described as an endogenous antagonist of GHSR. Here, we present study aimed at delineating the structural determinants required for LEAP2 activity toward We demonstrate entire sequence not necessary its actions. Indeed, N-terminal part alone confers binding to LEAP2. found...
G protein-coupled receptors (GPCRs) are integral membrane proteins that play a pivotal role in signal transduction. Understanding their dynamics is absolutely required to get clear picture of how signaling proceeds. Molecular characterization GPCRs isolated detergents nevertheless stumbles over the deleterious effect these compounds on receptor function and stability. We explored here potential styrene-maleic acid polymer solubilize directly from lipid environment. To this end, we used two...
The dynamic character of G protein-coupled receptors is essential to their function. However, the details how ligands stabilize a particular conformation selectively activate signaling pathway and proteins affect this conformational repertoire remain unclear. Using prototypical peptide-activated class A receptor (GPCR), ghrelin receptor, reconstituted as monomer into lipid discs labeled with fluorescent reporter, we demonstrate that ligand efficacy functional selectivity are directly related...
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...
Abstract Ghrelin is a potent orexigenic peptide hormone that acts through the growth secretagogue receptor (GHSR), G protein–coupled highly expressed in hypothalamus. In vitro studies have shown GHSR displays high constitutive activity, whose physiological relevance uncertain. As gene expression hypothalamus known to increase fasting conditions, we tested hypothesis activity at hypothalamic level drives fasting-induced hyperphagia. We found refed wild-type (WT) mice displayed robust...
Abstract Background Cachexia is a wasting condition associated with cancer types and, at the same time, serious and dose‐limiting side effect of chemotherapy. Skeletal muscle loss one main characteristics cachexia that significantly contributes to functional impairment. Calcium‐dependent signaling pathways are believed play an important role in skeletal decline observed cachexia, but whether intracellular calcium homeostasis affected this situation remains uncertain. Growth hormone...
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...
Ghrelin plays a central role in controlling major biological processes. As for other G protein-coupled receptor (GPCR) peptide agonists, the structure and dynamics of ghrelin bound to its remain obscure. Using combination solution-state NMR molecular modeling, we demonstrate that binding growth hormone secretagogue is accompanied by conformational change structures region, involving formation well-defined hydrophobic core. By comparing acylated nonacylated forms, conclude octanoyl chain...
ABSTRACT Systemic infusions of the orexigenic peptide ghrelin (GHR) increase dopamine levels within nucleus accumbens and augment cocaine‐stimulated locomotion conditioned place preference in rats; observations that suggest an important role for GHR receptors (GHR‐Rs) drug reinforcement. In present studies, we examined development cocaine locomotor sensitization rats, sustaining either pharmacologic antagonism or genetic ablation GHR‐Rs. a study, adult male rats were injected (i.p.) with 0,...
Ghrelin targets the arcuate nucleus, from where growth hormone releasing (GHRH) neurones trigger GH secretion. This hypothalamic nucleus also contains neuropeptide Y (NPY) neurons which play a master role in effect of ghrelin on feeding. Interestingly, connections between NPY and GHRH have been reported, leading to hypothesis that axis feeding circuits might be co-regulated by ghrelin.Here, we show stimulates firing rate identified neurons, transgenic GHRH-GFP mice. stimulation is prevented...
A single tool for early detection, accurate staging, and personalized treatment of prostate cancer (PCa) would be a major breakthrough in the field PCa. Gastrin-releasing peptide receptor (GRPR) targeting peptides are promising probes theranostic approach PCa overexpressing GRPR. However, successful application small is often hampered by their fast vivo degradation proteolytic enzymes, such as neutral endopeptidase (NEP). Here we show first time that co-injection NEP inhibitor...
Breast cancer (BC) consists of multiple subtypes defined by various molecular characteristics, for instance, estrogen receptor (ER) expression. Methods visualizing BC include mammography, MR imaging, ultrasound, and nuclear medicine-based methods such as (99m)Tc-sestamibi (18)F-FDG PET, unfortunately all lacking specificity. Peptide scintigraphy peptide radionuclide therapy are successfully applied imaging somatostatin receptor-expressing neuroendocrine tumors using radioligands. On the...
The growth hormone secretagogue receptor (GHSR) is a G protein-coupled that highly expressed in the central nervous system. GHSR acts as for ghrelin and liver-expressed antimicrobial peptide 2 (LEAP2), which blocks ghrelin-evoked activity. also displays ligand-independent activity, including high constitutive activity signals absence of reduced by LEAP2. modulates variety food intake-related behaviours, binge eating. Previously, we reported GHSR-deficient mice daily time-limited exposed to...
Abstract The membrane is an integral component of the G protein-coupled receptor signaling machinery. Here we demonstrate that lipids regulate efficacy and selectivity ghrelin GHSR through specific interactions bulk effects. We find PIP2 shifts conformational equilibrium away from its inactive state, favoring basal agonist-induced protein activation. This occurs because a preferential binding to intracellular sites in active state. Another lipid, GM3, also binds favors activation, but mostly...