Papers by Sylvie Claeysen
JoVE Video Dataset
Journal of Visualized Experiments, Sep 8, 2014
EMBO Reports, 2001
) are responsible for certain human diseases. A consistent structural description of the molecula... more ) are responsible for certain human diseases. A consistent structural description of the molecular change underlying the conversion of GPCRs from an inactive R state to an active R* state is lacking. Here, we show that a series of constitutively active 5-HT 4 receptors (mutated or truncated in the C-terminal and the third intracellular loop) were characterized by an increase in their denaturation rate at 55°C. The thermal denaturation kinetics were monophasic, suggesting that we were measuring mainly the denaturation rate of R*. Analysis of these kinetics revealed that constitutively active C-terminal domain mutants, were due to a change in the J constant governing the R/R* equilibrium. However, the constitutive activity of the receptor mutated within the third intracellular loop was the result of both a change in the allosteric J constant and a change in the R* conformation.
Molecular Biology of the Cell, Jun 1, 2007
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific r... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Handbook of Behavioral Neuroscience, 2020
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific r... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
New insights in molecular aspects of Alzheimer’s disease. Conférencière invitée
HAL (Le Centre pour la Communication Scientifique Directe), Mar 13, 2013
International audienc
Time dependent vascular pericyte changes in a genetic model of Alzheimer’s disease
HAL (Le Centre pour la Communication Scientifique Directe), Jul 6, 2015
International audienc
Longitudinal cerebrovascular changes in a genetic model of Alzheimer’s disease
HAL (Le Centre pour la Communication Scientifique Directe), Mar 18, 2015
International audienc
We are creating families of designer G protein– coupled receptors (GPCRs) to allow for precise sp... more We are creating families of designer G protein– coupled receptors (GPCRs) to allow for precise spatiotemporal control of GPCR signaling in vivo. These engineered GPCRs, called receptors activated solely by synthetic ligands (RASSLs), are unresponsive to endogenous ligands but can be activated by nanomolar concentrations of pharmacologically inert, drug-like small molecules. Currently, RASSLs exist for the three major GPCR signaling pathways (G s , G i and G q ). We review these advances here to facilitate the use of these powerful and diverse tools.
Impact du microbiote intestinal dans un modèle murin de maladie d’Alzheimer
HAL (Le Centre pour la Communication Scientifique Directe), Jun 8, 2016
International audienc
Microbiote intestinal et maladie d’Alzheimer : une piste stratégique pour des biomarqueurs innovants ?
HAL (Le Centre pour la Communication Scientifique Directe), Jun 14, 2017
International audienc
Caractérisation immunohistologique de la pathologie amyloïde et des symptômes associés dans un modèle murin dela maladie d'Alzheimer. (Conférencière invitée)
Le Centre pour la Communication Scientifique Directe - HAL - Inria, Jun 11, 2015
International audienc
How do synthetic agonists and inverse agonists modify the conformational states of the 5-HT4 receptor?
Le Centre pour la Communication Scientifique Directe - HAL - memSIC, Jul 12, 2008
International audienc
CCDC 1045006: Experimental Crystal Structure Determination
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
In addition to their role in desensitization and internalization of G protein-coupled receptors (... more In addition to their role in desensitization and internalization of G protein-coupled receptors (GPCRs), b-arrestins are essential scaffolds linking GPCRs to Erk1/2 signaling. However, their role in GPCR-operated Erk1/2 activation differs between GPCRs and the underlying mechanism remains poorly characterized. Here, we show that activation of serotonin 5-HT 2C receptors, which engage Erk1/2 pathway via a b-arrestin-dependent mechanism, promotes MEKdependent b-arrestin2 phosphorylation at Thr 383 , a necessary step for Erk recruitment to the receptor/b-arrestin complex and Erk activation. Likewise, Thr 383 phosphorylation is involved in barrestin-dependent Erk1/2 stimulation elicited by other GPCRs such as b 2-adrenergic, FSH and CXCR4 receptors, but does not affect the b-arrestin-independent Erk1/2 activation by 5-HT 4 receptor. Collectively, these data show that b-arrestin2 phosphorylation at Thr 383 underlies barrestin-dependent Erk1/2 activation by GPCRs.
Molecules, 2019
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease which is still poorly unde... more Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease which is still poorly understood. The drugs currently used against AD, mainly acetylcholinesterase inhibitors (AChEI), are considered clinically insufficient and are responsible for deleterious side effects. AChE is, however, currently receiving renewed interest through the discovery of a chaperone role played in the pathogenesis of AD. But AChE could also serve as an activating protein for pleiotropic prodrugs. Indeed, inhibiting central AChE with brain-penetrating designed carbamates which are able to covalently bind to the enzyme and to concomitantly liberate active metabolites in the brain could constitute a clinically more efficient approach which, additionally, is less likely to cause peripheral side effects. We aim in this article to pave the road of this new avenue with an in vitro and in vivo study of pleiotropic prodrugs targeting both the 5-HT4 receptor and AChE, in order to display a neuroprotective a...
Neuropharmacology, Jan 24, 2017
Alzheimer's disease (AD) is the main cause of dementia and a major health issue worldwide. Th... more Alzheimer's disease (AD) is the main cause of dementia and a major health issue worldwide. The complexity of the pathology continues to challenge its comprehension and the implementation of effective treatments. In the last decade, a number of possible targets of intervention have been pointed out, among which the stimulation of 5-HT4 receptors (5-HT4Rs) seems very promising. 5-HT4R agonists exert pro-cognitive effects, inhibit amyloid-β peptide (Aβ) production and therefore directly and positively impact AD progression. In the present work, we investigated the effects of RS 67333, a partial 5-HT4R agonist, after chronic administration in the 5xFAD mouse model of AD. 5xFAD male mice and their wild type (WT) male littermates received either RS 67333 or vehicle solution i.p., twice a week, for 2 or 4 months. Cognitive performance was evaluated in a hippocampal-dependent behavioral task, the olfactory tubing maze (OTM). Mice were then sacrificed to evaluate the metabolism of the am...
Faculty Reviews, 2021
Serotonin (5-HT) appeared billions of years before 5-HT receptors and synapses. It is thus not su... more Serotonin (5-HT) appeared billions of years before 5-HT receptors and synapses. It is thus not surprising that 5-HT can control biological processes independently of its receptors. One example is serotonylation, which consists of covalent binding of 5-HT to the primary amine of glutamine. Over the past 20 years, serotonylation has been involved in the regulation of many signaling mechanisms. One of the most striking examples is the recent evidence that serotonylation of histone H3 constitutes an epigenetic mark. However, the pathophysiological role of histone H3 serotonylation remains to be discovered. All but one of the 5-HT receptors are G-protein-coupled receptors (GPCRs). The signaling pathways they control are finely tuned, and new, unexpected regulatory mechanisms are being uncovered continuously. Some 5-HT receptors (5-HT 2C , 5-HT 4 , 5-HT 6 , and 5-HT 7) signal through mechanisms that require neither G-proteins nor β-arrestins, the two classical and almost universal GPCR signal transducers. 5-HT 6 receptors are constitutively activated via their association with intracellular GPCR-interacting proteins (GIPs), including neurofibromin 1, cyclin-dependent kinase 5 (Cdk5), and G-protein-regulated inducer of neurite outgrowth 1 (GPRIN1). Interactions of 5-HT 6 receptor with Cdk5 and GPRIN1 are not concomitant but occur sequentially and play a key role in dendritic tree morphogenesis. Furthermore, 5-HT 6 receptor-mediated G-protein signaling in neurons is different in the cell body and primary cilium, where it is modulated by smoothened receptor activation. Finally, 5-HT 2A receptors form heteromers with mGlu 2 metabotropic glutamate receptors. This heteromerization results in a specific phosphorylation of mGlu 2 receptor on a serine residue (Ser 843) upon agonist stimulation of 5-HT 2A or mGlu 2 receptor. mGlu 2 receptor phosphorylation on Ser 843 is an essential step in engagement of G i/o signaling not only upon mGlu 2 receptor activation but also following 5-HT 2A receptor activation, and thus represents a key molecular event underlying functional crosstalk between both receptors.
Modulation du microbiote intestinal comme nouvelle voie thérapeutique contre la maladie d’Alzheimer
Revue Neurologique
Activation Chronique Du Recepteur De La Serotonine De Type 4 Effet Preventif Dans Un Model Murin De La Maladied Alzheimer Conferenciere Invitee
Réunion francophone sur la maladie d'Alzheimer, Jun 11, 2014
International audienc
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Papers by Sylvie Claeysen