Pascale Crépieux

Physiologie de la Reproduction et des Comportements

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ÉR

Éric Reiter

Physiologie de la Reproduction et des Comportements

Anne Poupon

Centre National de la Recherche Scientifique

Florian Guillou

Physiologie de la Reproduction et des Comportements

Astrid Musnier

Physiologie de la Reproduction et des Comportements

Thomas Bourquard

Physiologie de la Reproduction et des Comportements

Thomas Boulo

Physiologie de la Reproduction et des Comportements

Christophe Gauthier

Laboratoire Interdisciplinaire des Environnements Continentaux

Romain Yvinec

Physiologie de la Reproduction et des Comportements

Gilles Bruneau

Physiologie de la Reproduction et des Comportements

Guillaume Durand

École Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine

Cooperative Institutions

Centre National de la Recherche Scientifique

174

Physiologie de la Reproduction et des Comportements

107

Université de Tours

102

Inserm

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

Institut National de la Recherche Agronomique

Institut Français du Cheval et de l'Équitation

Institut Pasteur de Lille

Biologie des Oiseaux et Aviculture

Institut de Biologie de Lille

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Unraveling the molecular architecture of a G protein-coupled receptor/β-arrestin/Erk module complex

Scientific Reports (2015)

Thomas Bourquard Flavie Landomiel Éric Reiter Pascale Crépieux David W. Ritchie

Abstract β-arrestins serve as signaling scaffolds downstream of G protein-coupled receptors and thus play a crucial role in a plethora of cellular processes. Although it is largely accepted that the ability of β-arrestins to interact simultaneously with many protein partners is key in G protein-independent signaling of GPCRs, only the precise knowledge of these multimeric arrangements will allow a full understanding of the dynamics of these interactions and their functional consequences. However, current experimental procedures for the determination of the three-dimensional structures of protein-protein complexes are not well adapted to analyze these short-lived, multi-component assemblies. We propose a model of the receptor/β-arrestin/Erk1 signaling module, which is consistent with most of the available experimental data. Moreover, for the β-arrestin/Raf1 and the β-arrestin/ERK interactions, we have used the model to design interfering peptides and shown that they compete with both partners, hereby demonstrating the validity of the predicted interaction regions.

Arrestin

Component (thermodynamics)

10.1038/srep10760

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Citations (49)

Taxol selectively blocks microtubule dependent NF-κB activation by phorbol ester via inhibition of IκBα phosphorylation and degradation

Oncogene (1999)

W. J. Spencer Hakju Kwon Pascale Crépieux Nicole Leclerc Rongtuan Lin

Nocodazole

IκBα

Phorbol

10.1038/sj.onc.1202335

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Citations (53)

Human Monocytic Cell Lines Transformed In Vitro by Epstein-Barr Virus Display a Type II Latency and LMP-1-Dependent Proliferation

Journal of Virology (2002)

E. Masy Éric Adriaenssens Claire Montpellier Pascale Crépieux Alexandra Mougel

ABSTRACT Epstein-Barr virus (EBV) classically infects and transforms B lymphocytes in vitro, yielding lymphoblastoid cell lines (LCLs). In contrast to other herpesviruses, EBV is not described as an infectious agent for monocytes. However, recent papers described in vitro infection of monocytes leading to abortive or transient viral expression. In the present study, we report the characterization of E1, a monocytic cell line infected and transformed by EBV. This cell line was derived from an LCL by a drastic electroporation and selection of neomycin-resistant cells, unfavorable to B-cell outgrowth. E1 expressed surface molecules of monocytic lineage (CD14, major histocompatibility complex class II, and CD80) and the c- fms gene, a highly specific marker for the monocytic lineage. This cell line is able to phagocytose and secrete proinflammatory monokines tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-8. E1 cells are tumorigenic after injection in nude mice, and a monocytic cell line obtained from one of these tumors (TE1) displayed immunophenotype and functional properties similar to those of E1. We detected the presence of the EBV genome in both cell lines, as well as expression of the EBNA-1 and LMP-1 , but not EBNA-2 , viral genes, characteristic of a type II latency. LMP-1 influences the phenotype of these monocytic cell lines, as demonstrated by down-regulation of cell proliferation and membrane intercellular adhesion molecule 1 expression due to an LMP-1 antisense strategy. This is the first description of a latently infected human monocytic cell line and the first direct demonstration of an instrumental role for LMP-1 in the proliferation of EBV-transformed cell lines expressing a type II latency.

10.1128/jvi.76.13.6460-6472.2002

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Citations (34)

A single domain intrabody targeting the follicle-stimulating hormone receptor (FSHR) impacts FSH-induced G protein-dependent signalling

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Pauline Raynaud Vinesh Jugnarain Océane Vaugrente Amandine Vallet Thomas Boulo

Abstract Intracellular variable fragments from heavy-chain antibody from camelids (intra-VHH) have been successfully used as chaperones to solve the 3D structure of active G protein-coupled receptors bound to their transducers. However, their effect on signalling has been poorly explored, although they may provide a better understanding on the relationships between receptor conformation and activity. Here, we isolated and characterized iPRC1, the first intra-VHH recognizing a member of the large glycoprotein hormone receptors family, the follicle-stimulating hormone receptor (FSHR). This intra-VHH recognizes the FSHR 3 rd intracellular loop and decreases cAMP production in response to FSH, without altering Gαs recruitment. Hence, iPRC1 behaves as an allosteric modulator and provides a new tool to complete structure/activity studies performed so far on this receptor.

Follicle-stimulating hormone receptor

10.1101/2023.08.07.552286

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Citations (1)

Gonadotropin receptors and their modulation by intracellular nanobodies

Pascale Crépieux

Modulation (music)

Source

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Citations (0)

A single domain intrabody as a novel tool to bias the subcellular trafficking of the follicle-stimulating hormone receptor

bioRxiv (Cold Spring Harbor Laboratory) (2025)

Pauline Raynaud J Gourdon Vinesh Jugnarain L. Berthet Frédéric Jean‐Alphonse

Intracellular variable fragments from heavy-chain only antibodies of camelids (intra-VHH) have been successfully used for their stabilizing properties to solve the 3D structure of active G protein-coupled receptors (GPCRs) bound to their cognate transducers. They also provide tools to link a given conformation of a GPCR to the signalling network engaged, thus allowing extensive structure/activity studies. Recently, they have been instrumental in tracking active GPCRs in various subcellular compartments. Here, we report the isolation and characterization of iPRC2, an intra-VHH recognizing the 1st and 3rd intracellular loops of the FSHR, but not of the luteinizing hormone/choriogonadotropin receptor close relative. Its expression in the cell decreases the cAMP production in response to hormone binding, and requires G𝛼s for optimal interaction with the receptor. Importantly, iPRC2 increases the FSHR accumulation in the early endosomes, and consequently, diminishes its recycling to the cell surface. Hence, in contrast to previously described intra-VHH that disclose active GPCR intracellular location, iPRC2 provokes per se a location bias, through its ability to reroute the FSHR. Thus, it is an innovative tool to examine the functional consequences of GPCR accumulation in various sub-cellular compartments.

Follicle-stimulating hormone receptor

10.1101/2025.02.13.638052

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Citations (0)

Effect of the social environment on olfaction and social skills in wild-type and a mouse model of autism

Translational Psychiatry (2024)

Caroline Gora Ana Dudas Lucas Court Anil Annamneedi Gaëlle Lefort

Autism spectrum disorders (ASD) are complex, polygenic and heterogenous neurodevelopmental conditions. The severity of autism-associated variants is influenced by environmental factors, particularly social experiences during the critical neurodevelopmental period. While early behavioral interventions have shown efficacy in some children with autism, pharmacological support for core features — impairments in social interaction and communication, and stereotyped or restricted behaviors — is currently lacking. In this study, we examined how the social environment influences both wild-type (WT) and Shank3 knockout (KO) mice, a model reflecting core autism-like traits. Our findings revealed that chronic social isolation enhanced social interaction and olfactory neuron responses in WT animals. Furthermore, it restored impairments in social novelty preference and olfactory function, as well as self-grooming in Shank3 KO mice. Conversely, an enriched social environment heightened social interest toward novel conspecifics in WT mice, but elicited the opposite effect in Shank3 KO mice. Notably, Shank3 KO mice displayed distinct social responses when exposed to WT or Shank3 KO mice. These results offer novel insights that could favor the implementation of behavioral interventions and inclusive classroom programs for children with ASD.

Social Behavior

Social identity approach

Neurodevelopmental disorder

Social Skills

10.1038/s41398-024-03174-6

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Citations (1)

Contributors

Elsevier eBooks (2021)

Ana Aranda Denise D. Belsham Véronique Bozon Maria Luisa Brandi Giulia Brigante

10.1016/b978-0-12-819801-8.09992-0

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Citations (0)

The N680S single nucleotide polymorphism (SNP) of the human FSH receptor (hFSHR) impacts on PKA nuclear translocation and CREB-dependent gene transcription

HAL (Le Centre pour la Communication Scientifique Directe) (2011)

Thibaud Tranchant Guillaume Durand Vincent Piketty Christophe Gauthier Pascale Crépieux

SNP

Transcription

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mRNA-Selective Translation Induced by FSH in Primary Sertoli Cells

Molecular Endocrinology (2012)

Astrid Musnier Kelly E. Leon Julia Morales Éric Reiter Thomas Boulo

Abstract FSH is a key hormonal regulator of Sertoli cell secretory activity, required to optimize sperm production. To fulfil its biological function, FSH binds a G protein-coupled receptor, the FSH-R. The FSH-R-transduced signaling network ultimately leads to the transcription or down-regulation of numerous genes. In addition, recent evidence has suggested that FSH might also regulate protein translation. However, this point has never been demonstrated conclusively yet. Here we have addressed this issue in primary rat Sertoli cells endogenously expressing physiological levels of FSH-R. We observed that, within 90 min of stimulation, FSH not only enhanced overall protein synthesis in a mammalian target of rapamycin-dependent manner but also increased the recruitment of mRNA to polysomes. m7GTP pull-down experiments revealed the functional recruitment of mammalian target of rapamycin and p70 S6 kinase to the 5′cap, further supported by the enhanced phosphorylation of one of p70 S6 kinase targets, the eukaryotic initiation factor 4B. Importantly, the scaffolding eukaryotic initiation factor 4G was also recruited, whereas eukaryotic initiation factor 4E-binding protein, the eukaryotic initiation factor 4E generic inhibitor, appeared to play a minor role in translational regulations induced by FSH, in contrast to what is generally observed in response to anabolic factors. This particular regulation of the translational machinery by FSH stimulation might support mRNA-selective translation, as shown here by quantitative RT-PCR amplification of the c-fos and vascular endothelial growth factor mRNA but not of all FSH target mRNA, in polysomal fractions. These findings add a new level of complexity to FSH biological roles in its natural target cells, which has been underappreciated so far.

Translational regulation

Eukaryotic initiation factor

Maturation promoting factor

EIF4E

10.1210/me.2011-1267

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Citations (32)