16 results on '"Catherine Mollereau"'
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2. Neanderthal and Denisova tooth protein variants in present-day humans.
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Clément Zanolli, Mathilde Hourset, Rémi Esclassan, and Catherine Mollereau
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Medicine ,Science - Abstract
Environment parameters, diet and genetic factors interact to shape tooth morphostructure. In the human lineage, archaic and modern hominins show differences in dental traits, including enamel thickness, but variability also exists among living populations. Several polymorphisms, in particular in the non-collagenous extracellular matrix proteins of the tooth hard tissues, like enamelin, are involved in dental structure variation and defects and may be associated with dental disorders or susceptibility to caries. To gain insights into the relationships between tooth protein polymorphisms and dental structural morphology and defects, we searched for non-synonymous polymorphisms in tooth proteins from Neanderthal and Denisova hominins. The objective was to identify archaic-specific missense variants that may explain the dental morphostructural variability between extinct and modern humans, and to explore their putative impact on present-day dental phenotypes. Thirteen non-collagenous extracellular matrix proteins specific to hard dental tissues have been selected, searched in the publicly available sequence databases of Neanderthal and Denisova individuals and compared with modern human genome data. A total of 16 non-synonymous polymorphisms were identified in 6 proteins (ameloblastin, amelotin, cementum protein 1, dentin matrix acidic phosphoprotein 1, enamelin and matrix Gla protein). Most of them are encoded by dentin and enamel genes located on chromosome 4, previously reported to show signs of archaic introgression within Africa. Among the variants shared with modern humans, two are ancestral (common with apes) and one is the derived enamelin major variant, T648I (rs7671281), associated with a thinner enamel and specific to the Homo lineage. All the others are specific to Neanderthals and Denisova, and are found at a very low frequency in modern Africans or East and South Asians, suggesting that they may be related to particular dental traits or disease susceptibility in these populations. This modern regional distribution of archaic dental polymorphisms may reflect persistence of archaic variants in some populations and may contribute in part to the geographic dental variations described in modern humans.
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- 2017
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3. Denatured G-protein coupled receptors as immunogens to generate highly specific antibodies.
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Franck Talmont, Lionel Moulédous, Jérôme Boué, Catherine Mollereau, and Gilles Dietrich
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Medicine ,Science - Abstract
G-protein coupled receptors (GPCRs) play a major role in a number of physiological and pathological processes. Thus, GPCRs have become the most frequent targets for development of new therapeutic drugs. In this context, the availability of highly specific antibodies may be decisive to obtain reliable findings on localization, function and medical relevance of GPCRs. However, the rapid and easy generation of highly selective anti-GPCR antibodies is still a challenge. Herein, we report that highly specific antibodies suitable for detection of GPCRs in native and unfolded forms can be elicited by immunizing animals against purified full length denatured recombinant GPCRs. Contrasting with the currently admitted postulate, our study shows that an active and well-folded GPCR is not required for the production of specific anti-GPCR antibodies. This new immunizing strategy validated with three different human GPCR (μ-opioid, κ-opioid, neuropeptide FF2 receptors) might be generalized to other members of the GPCR family.
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- 2012
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4. Hearing sensitivity of primates: recurrent and episodic positive selection in hair cells and stereocilia protein-coding genes
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Catherine Mollereau, Franklin Delehelle, Andreia Moreira, Hervé Luga, Sylvain Cussat-Blanc, Myriam Croze, Patricia Balaresque, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Real Expression Artificial Life (IRIT-REVA), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1)
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AcademicSubjects/SCI01140 ,Stereocilia (inner ear) ,primates ,[SDV]Life Sciences [q-bio] ,Sound perception ,Mechanotransduction, Cellular ,branch-site test ,positive selection ,biology.animal ,Hair Cells, Auditory ,Genetics ,otorhinolaryngologic diseases ,Animals ,Primate ,inner-ear-expressed genes ,[INFO]Computer Science [cs] ,Gene conversion ,Gene ,Ecology, Evolution, Behavior and Systematics ,Selection (genetic algorithm) ,stereocilia ,biology ,AcademicSubjects/SCI01130 ,Evolutionary biology ,hearing ,Human genome ,PCDH15 ,Research Article - Abstract
The large spectrum of hearing sensitivity observed in primates results from the impact of environmental and behavioral pressures to optimize sound perception and localization. Although evidence of positive selection in auditory genes has been detected in mammals including in Hominoids, selection has never been investigated in other primates. We analyzed 123 genes highly expressed in the inner ear of 27 primate species and tested to what extent positive selection may have shaped these genes in the order Primates tree. We combined both site and branch-site tests to obtain a comprehensive picture of the positively selected genes (PSGs) involved in hearing sensitivity, and drew a detailed description of the most affected branches in the tree. We chose a conservative approach, and thus focused on confounding factors potentially affecting PSG signals (alignment, GC-biased gene conversion, duplications, heterogeneous sequencing qualities). Using site tests, we showed that around 12% of these genes are PSGs, an α selection value consistent with average human genome estimates (10–15%). Using branch-site tests, we showed that the primate tree is heterogeneously affected by positive selection, with the black snub-nosed monkey, the bushbaby, and the orangutan, being the most impacted branches. A large proportion of these genes is inclined to shape hair cells and stereocilia, which are involved in the mechanotransduction process, known to influence frequency perception. Adaptive selection, and more specifically recurrent adaptive evolution, could have acted in parallel on a set of genes (ADGRV1, USH2A, PCDH15, PTPRQ, and ATP8A2) involved in stereocilia growth and the whole complex of bundle links connecting them, in species across different habitats, including high altitude and nocturnal environments.
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- 2021
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5. Pharmacological insight into the activation of the human Neuropeptide FF2 receptor
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Catherine Mollereau, Franck Talmont, Remi Veneziano, Jean-Marie Zajac, Lionel Moulédous, Gilles Dietrich, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
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Receptors, Neuropeptide ,Physiology ,G protein ,Neuropeptide ,030209 endocrinology & metabolism ,Biochemistry ,Adenylyl cyclase ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Structure-Activity Relationship ,0302 clinical medicine ,Endocrinology ,Cricetinae ,Aspartic acid ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Amino Acid Sequence ,Receptor ,Cells, Cultured ,ComputingMilieux_MISCELLANEOUS ,G protein-coupled receptor ,C-terminus ,Neuropeptides ,Cell biology ,Analgesics, Opioid ,chemistry ,Mutagenesis ,Signal transduction ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
International audience; The neuropeptide FF2 (NPFF 2) receptor, predominantly expressed in the central nervous system, plays an important role in the modulation of sensory input and opioid analgesia, as well as in locomotion, feeding, intestinal motility, reward, and the control of obesity. The NPFF 2 receptor belongs to the RFamide peptide receptor family and to the G protein coupled receptor (GPCR) super family, but contrary to many other class A GPCRs, no 3D structure has been solved. Thus, it is essential to perform mutagenesis to gain information on the fine functioning of the NPFF 2 receptor. In this study, we examined the role of aspartic acid (D) from the "D/ERY/F" motif found in the second intracellular loop (ICL2) and the role of the C-terminal end of the receptor in ligand binding and signal transduction. We found that mutation D3.49A does not impair binding capacities but inhibits G protein activation as well as adenylyl cyclase regulation. Truncation of the C terminal part of the receptor has different effects depending on the position of truncation. When truncation was realized downstream of the putative acylation site, ligand binding and signal transduction capabilities were not lost, contrary to total deletion of the C terminus, which totally impairs the activity of the receptor.
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- 2020
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6. Ancient tooth proteomes
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Mathilde, Hourset, Froment, Carine, Zanolli, Clément, Nancy, Saenz, Claire, Willmann, Rémi, Esclassan, Catherine, Thèves, Burlet-Schiltz, Odile, Catherine, Mollereau, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
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[SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory ,[SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology ,[SDU.STU.PG]Sciences of the Universe [physics]/Earth Sciences/Paleontology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2017
7. Ancient tooth proteomes
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Froment, Carine, Hourset, Mathilde, Saenz, Nancy, Claire, Willmann, Stella, Alexandre, Mouton-Barbosa, Emmanuelle, Zanolli, Clément, Rémi, Esclassan, Catherine, Thèves, Burlet-Schiltz, Odile, Catherine, Mollereau, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
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[SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory ,[SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology ,[SDU.STU.PG]Sciences of the Universe [physics]/Earth Sciences/Paleontology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2017
8. Development of a Peptidomimetic Antagonist of Neuropeptide FF Receptors for the Prevention of Opioid-Induced Hyperalgesia
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Benoit Petit-Demoulière, Jean-Paul Humbert, Martine Schmitt, Frédéric Simonin, Emilie Laboureyras, Elodie Schneider, Patrick Wagner, Catherine Mollereau, Jean-Jacques Bourguignon, Isabelle Bertin, Guy Simonnet, Séverine Schneider, Frédéric Bihel, Laboratoire d'Innovation Thérapeutique (LIT), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS)
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Male ,Ornithine ,Pain Threshold ,Receptors, Neuropeptide ,Time Factors ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,Chemical Phenomena ,Arginine ,Physiology ,Peptidomimetic ,Cognitive Neuroscience ,Pharmacology ,Tritium ,Biochemistry ,Rats, Sprague-Dawley ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cyclic AMP ,medicine ,Animals ,Humans ,Neuropeptide FF ,Receptor ,Opioid-induced hyperalgesia ,Chemistry ,Antagonist ,Cell Biology ,General Medicine ,Rats ,3. Good health ,Analgesics, Opioid ,Fentanyl ,HEK293 Cells ,Hyperalgesia ,Microsomes, Liver ,Peptidomimetics ,medicine.symptom ,Protein Binding - Abstract
Through the development of a new class of unnatural ornithine derivatives as bioisosteres of arginine, we have designed an orally active peptidomimetic antagonist of neuropeptide FF receptors (NPFFR). Systemic low-dose administration of this compound to rats blocked opioid-induced hyperalgesia, without any apparent side-effects. Interestingly, we also observed that this compound potentiated opioid-induced analgesia. This unnatural ornithine derivative provides a novel therapeutic approach for both improving analgesia and reducing hyperalgesia induced by opioids in patients being treated for chronic pain.
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- 2015
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9. Heterologous Regulation of Mu-Opioid (MOP) Receptor Mobility in the Membrane of SH-SY5Y Cells*
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Laurence Salomé, Anne Combedazou, Lionel Moulédous, Evert Haanappel, Kevin Carayon, Catherine Mollereau, and Serge Mazères
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Receptors, Neuropeptide ,medicine.drug_class ,Receptors, Opioid, mu ,Heterologous ,Biology ,Biochemistry ,Clonidine ,Protein–protein interaction ,Diffusion ,Bimolecular fluorescence complementation ,Opioid receptor ,Receptors, Adrenergic, alpha-2 ,Membrane Biology ,Cell Line, Tumor ,medicine ,Humans ,Neuropeptide Y ,Neuropeptide FF ,Receptor ,Molecular Biology ,Fluorescent Dyes ,Neurons ,Cell Membrane ,Fluorescence recovery after photobleaching ,Cell Biology ,Receptor Cross-Talk ,Enkephalin, Ala(2)-MePhe(4)-Gly(5) ,Analgesics, Opioid ,Protein Transport ,Gene Expression Regulation ,Biophysics ,μ-opioid receptor ,Protein Multimerization ,Oligopeptides ,Fluorescence Recovery After Photobleaching ,Signal Transduction - Abstract
The dynamic organization of G protein-coupled receptors in the plasma membrane is suspected of playing a role in their function. The regulation of the diffusion mode of the mu-opioid (MOP) receptor was previously shown to be agonist-specific. Here we investigate the regulation of MOP receptor diffusion by heterologous activation of other G protein-coupled receptors and characterize the dynamic properties of the MOP receptor within the heterodimer MOP/neuropeptide FF (NPFF2) receptor. The data show that the dynamics and signaling of the MOP receptor in SH-SY5Y cells are modified by the activation of α2-adrenergic and NPFF2 receptors, but not by the activation of receptors not described to interact with the opioid receptor. By combining, for the first time, fluorescence recovery after photobleaching at variable radius experiments with bimolecular fluorescence complementation, we show that the MOP/NPFF2 heterodimer adopts a specific diffusion behavior that corresponds to a mix of the dynamic properties of both MOP and NPFF2 receptors. Altogether, the data suggest that heterologous regulation is accompanied by a specific organization of receptors in the membrane.
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- 2014
10. A Switch of G Protein-Coupled Receptor Binding Preference from Phosphoinositide 3-Kinase (PI3K)–p85 to Filamin A Negatively Controls the PI3K Pathway
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Catherine Mollereau, Corinne Bousquet, Stefan Schulz, Nathalie Saint-Laurent, Jens Lättig, Souad Najib, Jean-Pierre Estève, Christiane Susini, Daniel Fourmy, Elisa Boutet-Robinet, Stéphane Pyronnet, Schulz, Stefan, Boutet-Robinet, Elisa, MOLLEREAU, Catherine, BOUSQUET, Corinne, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Kastler Brossel (LKB (Jussieu)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institute of Pharmacology and Toxicology, Jena University Hospital, Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), ProdInra, Archive Ouverte, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Toxicologie Alimentaire (UTA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre de Recherche en Cancérologie de Toulouse (CRCT), UMR 1037, Université Paul Sabatier - Toulouse 3 ( UPS ), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR31-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Kastler Brossel ( LKB (Jussieu) ), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris ( FRDPENS ), Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Toxicologie Alimentaire ( UTA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut de Pharmacologie et de Biologie Structurale, UMR 5089, Centre National de la Recherche Scientifique ( CNRS ), INSERM UMR1037-Cancer Research Center of Toulouse, Toulouse, France, Centre de Recherche en Cancérologie de Toulouse ( CRCT ), and Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM )
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Filamins ,[SDV]Life Sciences [q-bio] ,macromolecular substances ,Biology ,Filamin ,Binding, Competitive ,Cell Line ,Receptors, G-Protein-Coupled ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Contractile Proteins ,FLNA ,Animals ,Phosphorylation ,Molecular Biology ,030304 developmental biology ,G protein-coupled receptor ,0303 health sciences ,Phosphoinositide 3-kinase ,Binding Sites ,[ SDV ] Life Sciences [q-bio] ,Microfilament Proteins ,Tyrosine phosphorylation ,Cell Biology ,Articles ,Ligand (biochemistry) ,Cell biology ,[SDV] Life Sciences [q-bio] ,Class Ia Phosphatidylinositol 3-Kinase ,Protein Subunits ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Signal transduction ,biological phenomena, cell phenomena, and immunity ,hormones, hormone substitutes, and hormone antagonists ,Protein Binding ,Signal Transduction - Abstract
Frequent oncogenic alterations occur in the phosphoinositide 3-kinase (PI3K) pathway, urging identification of novel negative controls. We previously reported an original mechanism for restraining PI3K activity, controlled by the somatostatin G protein-coupled receptor (GPCR) sst2 and involving a ligand-regulated interaction between sst2 with the PI3K regulatory p85 subunit. We here identify the scaffolding protein filamin A (FLNA) as a critical player regulating the dynamic of this complex. A preexisting sst2-p85 complex, which was shown to account for a significant basal PI3K activity in the absence of ligand, is disrupted upon sst2 activation. FLNA was here identified as a competitor of p85 for direct binding to two juxtaposed sites on sst2. Switching of GPCR binding preference from p85 toward FLNA is determined by changes in the tyrosine phosphorylation of p85- and FLNA-binding sites on sst2 upon activation. It results in the disruption of the sst2-p85 complex and the subsequent inhibition of PI3K. Knocking down FLNA expression, or abrogating FLNA recruitment to sst2, reversed the inhibition of PI3K and of tumor growth induced by sst2. Importantly, we report that this FLNA inhibitory control on PI3K can be generalized to another GPCR, the mu opioid receptor, thereby providing an unprecedented mechanism underlying GPCR-negative control on PI3K.
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- 2012
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11. Neuropeptide FF-sensitive confinement of mu opioid receptor does not involve lipid rafts in SH-SY5Y cells
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Lionel Moulédous, Jérémie Neasta, Soren Merker, Jean-Marie Zajac, Catherine Mollereau, Benoît Roux, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and ANR-06-NEUR-0041,Pain and RF-amides,Rôle des récepteurs de neuropeptides RF-amides mammifères dans la modulation de la douleur et la tolérance aux effets analgésiques des opiacés.(2006)
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Receptors, Neuropeptide ,SH-SY5Y ,Detergents ,Biophysics ,Receptors, Opioid, mu ,MESH: Membrane Microdomains ,Neuropeptide FF receptor ,MESH: Receptors, Opioid, mu ,Cell Fractionation ,Biochemistry ,Cell Line ,03 medical and health sciences ,Membrane Microdomains ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Neuropeptide FF ,Receptor ,Molecular Biology ,Lipid raft ,030304 developmental biology ,0303 health sciences ,MESH: Humans ,Chemistry ,MESH: Receptors, Neuropeptide ,030302 biochemistry & molecular biology ,Fluorescence recovery after photobleaching ,Cell Biology ,MESH: Cell Line ,MESH: Oligopeptides ,MESH: Cell Fractionation ,Cell fractionation ,μ-opioid receptor ,Oligopeptides ,MESH: Fluorescence Recovery After Photobleaching ,Fluorescence Recovery After Photobleaching ,MESH: Detergents - Abstract
Mu opioid (MOP) receptor activation can be functionally modulated by stimulation of Neuropeptide FF 2 (NPFF(2)) G protein-coupled receptors. Fluorescence recovery after photobleaching experiments have shown that activation of the NPFF(2) receptor dramatically reduces the fraction of MOP receptors confined in microdomains of the plasma membrane of SH-SY5Y neuroblastoma cells. The aim of the present work was to assess if the direct observation of receptor compartmentation by fluorescence techniques in living cells could be related to indirect estimation of receptor partitioning in lipid rafts after biochemical fractionation of the cell. Our results show that MOP receptor distribution in lipid rafts is highly dependent upon the method of purification, questioning the interpretation of previous data regarding MOP receptor compartmentation. Moreover, the NPFF analogue 1DMe does not modify the distribution profile of MOP receptors, clearly demonstrating that membrane fractionation data do not correlate with direct measurement of receptor compartmentation in living cells.
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- 2008
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12. RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia
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Emilie Laboureyras, Frédéric Simonin, Brigitte L. Kieffer, Jean-Paul Laulin, Marc Parmentier, Audrey Matifas, Jean-Jacques Bourguignon, Catherine Mollereau, David MacTavish, Guy Simonnet, Jack H. Jhamandas, Martine Schmitt, Patrick Laurent, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, and Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS)
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Receptors, Neuropeptide ,Neuropeptide FF receptor ,Adamantane ,Blood Pressure ,Pharmacology ,Ligands ,MESH: Analgesics, Opioid ,0302 clinical medicine ,MESH: Dipeptides ,Heart Rate ,Drug tolerance ,Chlorocebus aethiops ,MESH: Ligands ,MESH: Animals ,Neuropeptide FF ,MESH: Heart Rate ,Receptor ,0303 health sciences ,Multidisciplinary ,Molecular Structure ,Chemistry ,MESH: Receptors, Neuropeptide ,Chronic pain ,Sciences du Vivant [q-bio]/Biotechnologies ,Dipeptides ,Drug Tolerance ,MESH: Adamantane ,MESH: Blood Pressure ,Biological Sciences ,MESH: Amides ,3. Good health ,Analgesics, Opioid ,MESH: COS Cells ,Hyperalgesia ,COS Cells ,MESH: Heroin ,medicine.symptom ,medicine.drug ,MESH: Rats ,MESH: Drug Tolerance ,MESH: Molecular Structure ,03 medical and health sciences ,medicine ,Animals ,Humans ,030304 developmental biology ,MESH: Humans ,Antagonist ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,medicine.disease ,Amides ,MESH: Hyperalgesia ,MESH: Cercopithecus aethiops ,Rats ,Heroin ,Opioid ,030217 neurology & neurosurgery - Abstract
International audience; Neuropeptide FF (NPFF) has been proposed to play a role in pain modulation, opioid tolerance, and several other physiological processes. However, pharmacological agents that would help define physiological roles for this peptide are still missing. Here we report the discovery of a potent and selective NPFF receptor antagonist, RF9, that can be administered systemically. This compound does not show any effects by itself but can block efficiently the increase in blood pressure and heart rate evoked by NPFF. When chronically coinjected with heroin, RF9 completely blocks the delayed and long-lasting paradoxical opioid-induced hyperalgesia and prevents the development of associated tolerance. Our data indicate that NPFF receptors are part of a bona fide antiopioid system and that selective antagonists of these receptors could represent useful therapeutic agents for improving the efficacy of opioids in chronic pain treatment.
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- 2006
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13. Anti-analgesia of a selective NPFF2 agonist depends on opioid activity
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Christine Gouardères, Anne Roussin, Jean-Marie Zajac, Michel Roumy, Honoré Mazarguil, Catherine Mollereau, Fuschia Serre, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
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Agonist ,Receptors, Neuropeptide ,Carbachol ,medicine.drug_class ,Biophysics ,CHO Cells ,Pharmacology ,Biochemistry ,Body Temperature ,03 medical and health sciences ,Mice ,0302 clinical medicine ,In vivo ,Cell Line, Tumor ,Cricetinae ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Receptor ,Molecular Biology ,030304 developmental biology ,Injections, Intraventricular ,0303 health sciences ,Chemistry ,Chinese hamster ovary cell ,Brain ,Cell Biology ,Receptors, Muscarinic ,3. Good health ,Analgesics, Opioid ,Opioid ,Molecular Probes ,Systemic administration ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,030217 neurology & neurosurgery ,Intracellular ,medicine.drug ,Signal Transduction - Abstract
NPFF agonists designed to be selective NPFF(2) receptor probes were synthesized. D.Asn-Pro-(N-Me)Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH(2) (dNPA) displays a very high affinity (0.027nM) for NPFF(2) receptors transfected in CHO cells, and a very high selectivity with a discrimination ratio greater than 100 versus NPFF(1) receptors. dNPA acts as a potent and selective agonist in [(35)S]GTPgammaS binding experiments and inhibits intracellular cAMP production with the same efficacy as NPA-NPFF. In SH-SY5Y cells expressing NPFF(2) receptors dNPA, in the presence of carbachol, stimulates Ca(2+) release from the intracellular stores. In vivo, after intracerebroventricular injection dNPA increases body temperature in mice and reverses the morphine-induced analgesia. Also, dNPA displays anti-opioid activity after systemic administration. So far, dNPA exhibits the highest affinity and selectivity for NPFF(2) receptors and reveals that its behavioral anti-opioid activity depends on the degree of opioid-induced analgesia.
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- 2005
14. Nucleotide sequence of a human cannabinoid receptor cDNA
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Catherine Gerard, Catherine Mollereau, Gilbert Vassart, and Marc Parmentier
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Genetics ,Cannabinoid receptor ,Base Sequence ,Receptors, Drug ,Molecular Sequence Data ,Nucleic acid sequence ,DNA ,Molecular cloning ,Biology ,Rats ,chemistry.chemical_compound ,chemistry ,Complementary DNA ,Sequence Homology, Nucleic Acid ,Animals ,Humans ,Base sequence ,Receptor ,Receptors, Cannabinoid ,Gene - Published
- 1990
15. Different domains of the ORL1 and κ-opioid receptors are involved in recognition of nociceptin and dynorphin A
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Catherine Mollereau, Jean-Luc Butour, Christiane Moisand, Jean-Claude Meunier, and Sophie Lapalu
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Narcotics ,Stereochemistry ,medicine.drug_class ,Narcotic Antagonists ,Recombinant Fusion Proteins ,Biophysics ,Class C GPCR ,Endogeny ,CHO Cells ,Ligands ,Biochemistry ,Dynorphins ,Protein Structure, Secondary ,Nociceptin Receptor ,chemistry.chemical_compound ,Structural Biology ,Opioid receptor ,Cricetinae ,Genetics ,medicine ,Cyclic AMP ,Animals ,Humans ,Opioid peptide ,Receptor ,Molecular Biology ,Chemistry ,Receptors, Opioid, kappa ,Colforsin ,Structure-function relationship ,Dynorphin A ,Cell Biology ,Gain-of-function protein engineering ,Cell biology ,Nociceptin receptor ,Kinetics ,Opioid ,Opioid Peptides ,Receptors, Opioid ,Non-opioid–opioid hybrid receptor ,medicine.drug - Abstract
In order to gain further insight into the functional architecture of structurally related G protein-coupled receptors, the ORL1 (nociceptin) and opioid receptors, we have constructed chimeras of ORL1 and mu-, delta- and kappa-opioid receptors, and compared their binding and functional properties with those of the parent receptors. We find in particular that a ORL1-kappa-opioid (O-K) hybrid construct has retained high affinity for non-type-selective opiate ligands, and has acquired the ability to bind and respond to enkephalins and mu- and/or delta-opioid receptor-selective enkephalins analogs, thus behaving like a 'universal' opioid receptor. Most significantly however, whilst the ORL1 and kappa-opioid receptors display high binding preference (KD 0.1 vs. 100 nM) for their respective endogenous ligands, nociceptin and dynorphin A, the O-K chimeric receptor binds both nociceptin and dynorphin A, with high affinity (KD1 nM). Together, these data (i) add weight to the hypothesis that the extracellular loops of opioid receptors act as a filter for ligand selection, and (ii) demonstrate that different domains of the ORL1 and kappa-opioid receptors are involved in recognition of their endogenous peptide ligands.
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16. Phosphoproteomic analysis of the mouse brain mu-opioid (MOP) receptor
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Carine Froment, Stefan Schulz, Odile Burlet-Schiltz, Lionel Moulédous, and Catherine Mollereau
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Proteomics ,inorganic chemicals ,Molecular Sequence Data ,Receptors, Opioid, mu ,Biophysics ,Endogeny ,macromolecular substances ,Opioid ,Pharmacology ,Biochemistry ,environment and public health ,Mass Spectrometry ,Mice ,Structural Biology ,In vivo ,Genetics ,medicine ,Animals ,Amino Acid Sequence ,Phosphorylation ,Receptor ,Molecular Biology ,G protein-coupled receptor ,Chemistry ,G-protein coupled receptor (GPCR) ,Brain ,Proteomic ,Cell Biology ,Phosphoproteins ,Analgesics, Opioid ,enzymes and coenzymes (carbohydrates) ,bacteria ,μ-opioid receptor ,Etonitazene ,medicine.drug - Abstract
Many in vitro data have shown that the efficacy of several opioid drugs is correlated with differential mu-opioid (MOP) receptor phosphorylation. Label-free semiquantitative on-line nanoflow liquid chromatography–tandem mass spectrometry (nanoLC–MS/MS) analyses were performed to compare the endogenous MOP receptor phosphorylation patterns of mice administered with morphine, etonitazene and fentanyl. The analysis identified S363, T370 and S375 as phosphorylated residues in the carboxy-terminus. Only T370 and S375 were regulated by agonists, with a higher propensity to promote double phosphorylation for high efficacy agonists. Our study provides confirmation that differential agonist-driven multi-site phosphorylation of MOP receptor occurs in vivo and validate the use of MS to study endogenous GPCR phosphorylation.
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