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Journal articles
Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation
Pauline Scholler
1
Damien Nevoltris
2, 3
Dimitri de Bundel
1
Simon Bossi
4
David Moreno-Delgado
1
Xavier Rovira
1
Thor C Møller
1
Driss El Moustaine
1
Michaël Mathieu
1
Emilie Blanc
1
Heather Mclean
4
Elodie Dupuis
2
Gérard Mathis
2
Eric Trinquet
2
Hervé Daniel
4
Emmanuel Valjent
1
Daniel Baty
5
Patrick Chames
5
Philippe Rondard
1
Jean-Philippe Pin
1
Pauline Scholler 1
Author
Damien Nevoltris 2, 3
Author
Dimitri de Bundel 1
Author
Simon Bossi 4
Author
David Moreno-Delgado 1
Author
Xavier Rovira 1
Author
Thor C Møller 1
Author
Driss El Moustaine 1
Author
Gérard Mathis 2
Author
Eric Trinquet 2
Author
Hervé Daniel 4
Author
Emmanuel Valjent 1
Author IdHAL : emmanuel-valjent IdRef : https://www.idref.fr/174375522 ORCID : https://orcid.org/0000-0002-1034-606X
Daniel Baty 5
Author
Patrick Chames 5
Author IdHAL : patrick-chames ORCID : https://orcid.org/0000-0002-6104-6286
Philippe Rondard 1
Author
Jean-Philippe Pin 1
Author IdHAL : jean-philippe-pin ORCID : https://orcid.org/0000-0002-1423-345X
1
IGF - Institut de Génomique Fonctionnelle (141, Rue de la Cardonille 34094 Montpellier cedex 5 - France)
- UM - Université de Montpellier (163 rue Auguste Broussonnet - 34090 Montpellier - France)
- UM1 - Université Montpellier 1 (5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1191 (101, rue de Tolbiac, 75013 Paris - France)
- UM2 - Université Montpellier 2 - Sciences et Techniques (Place Eugène Bataillon - 34095 Montpellier cedex 5 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR5203 (France)
2
Cisbio Bioassays (Parc Technologique Marcel Boiteux BP 84175 30204 Bazgnols sur Cèze - France)
- Cisbio Bioassays (France)
3
CRCM - Département de radiologie [Institut Paoli Calmettes] (F-13009, Marseille - France)
4
NeuroPSI - Institut des Neurosciences Paris-Saclay (Centre National de la Recherche Scientifique, Unité Mixte de Recherche-9197 Université Paris-Sud
bâtiment 32 Campus de Recherche de Gif-sur-Yvette
1, avenue de la Terrasse
91198 Gif-sur-Yvette - France)
- UP11 - Université Paris-Sud - Paris 11 : UMR9497 (Bâtiment 300 - 91405 Orsay cedex - France)
- CNRS - Centre National de la Recherche Scientifique : UMR9197 (France)
5
CRCM - Centre de Recherche en Cancérologie de Marseille (27 bd Leï Roure, BP 300059
13273 Marseille Cedex 09 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7258 (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1068 (101, rue de Tolbiac, 75013 Paris - France)
- Institut Paoli-Calmettes : UMR7258 (France)
- AMU - Aix Marseille Université : UM105 (Aix-Marseille Université Jardins du Pharo 58 Boulevard Charles Livon 13284 Marseille cedex 7 - France)
Abstract : Antibodies have enormous therapeutic and biotechnology potential. G protein-coupled receptors (GPCRs), the main targets in drug development, are of major interest in antibody development programs. Metabotropic glutamate receptors are dimeric GPCRs that can control synaptic activity in a multitude of ways. Here we identify llama nanobodies that specifically recognize mGlu2 receptors, among the eight subtypes of mGluR subunits. Among these nanobodies, DN10 and 13 are positive allosteric modulators (PAM) on homodimeric mGlu2, while DN10 displays also a significant partial agonist activity. DN10 and DN13 have no effect on mGlu2-3 and mGlu2-4 heterodimers. These PAMs enhance the inhibitory action of the orthosteric mGlu2/mGlu3 agonist, DCG-IV, at mossy fiber terminals in the CA3 region of hippocampal slices. DN13 also impairs contextual fear memory when injected in the CA3 region of hippocampal region. These data highlight the potential of developing antibodies with allosteric actions on GPCRs to better define their roles in vivo.
Document type :
Journal articles
Complete list of metadatas
https://hal.archives-ouvertes.fr/hal-01672805
Contributor : Alain Perignon <>
Submitted on : Wednesday, December 27, 2017 - 11:53:50 AM
Last modification on : Thursday, February 25, 2021 - 12:17:05 PM
Contributor : Alain Perignon <>
Submitted on : Wednesday, December 27, 2017 - 11:53:50 AM
Last modification on : Thursday, February 25, 2021 - 12:17:05 PM
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Identifiers
- HAL Id : hal-01672805, version 1
- DOI : 10.1038/s41467-017-01489-1
- PUBMED : 29213077
Collections
CNRS | UNIV-AMU | BS | UNIV-MONTPELLIER | CRCM
Citation
Pauline Scholler, Damien Nevoltris, Dimitri de Bundel, Simon Bossi, David Moreno-Delgado, et al.. Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation. Nature Communications, Nature Publishing Group, 2017, 8 (1), pp.1967. ⟨10.1038/s41467-017-01489-1⟩. ⟨hal-01672805⟩
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