Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation. / Scholler, Pauline; Nevoltris, Damien; de Bundel, Dimitri; Bossi, Simon; Moreno-Delgado, David; Rovira, Xavier; Møller, Thor C; El Moustaine, Driss; Mathieu, Michaël; Blanc, Emilie; McLean, Heather; Dupuis, Elodie; Mathis, Gérard; Trinquet, Eric; Daniel, Hervé; Valjent, Emmanuel; Baty, Daniel; Chames, Patrick; Rondard, Philippe; Pin, Jean-Philippe.

In: Nature Communications, Vol. 8, No. 1, 06.12.2017, p. 1967.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Scholler, P, Nevoltris, D, de Bundel, D, Bossi, S, Moreno-Delgado, D, Rovira, X, Møller, TC, El Moustaine, D, Mathieu, M, Blanc, E, McLean, H, Dupuis, E, Mathis, G, Trinquet, E, Daniel, H, Valjent, E, Baty, D, Chames, P, Rondard, P & Pin, J-P 2017, 'Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation', Nature Communications, vol. 8, no. 1, pp. 1967. https://doi.org/10.1038/s41467-017-01489-1

APA

Scholler, P., Nevoltris, D., de Bundel, D., Bossi, S., Moreno-Delgado, D., Rovira, X., ... Pin, J-P. (2017). Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation. Nature Communications, 8(1), 1967. https://doi.org/10.1038/s41467-017-01489-1

Vancouver

Scholler P, Nevoltris D, de Bundel D, Bossi S, Moreno-Delgado D, Rovira X et al. Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation. Nature Communications. 2017 Dec 6;8(1):1967. https://doi.org/10.1038/s41467-017-01489-1

Author

Scholler, Pauline ; Nevoltris, Damien ; de Bundel, Dimitri ; Bossi, Simon ; Moreno-Delgado, David ; Rovira, Xavier ; Møller, Thor C ; El Moustaine, Driss ; Mathieu, Michaël ; Blanc, Emilie ; McLean, Heather ; Dupuis, Elodie ; Mathis, Gérard ; Trinquet, Eric ; Daniel, Hervé ; Valjent, Emmanuel ; Baty, Daniel ; Chames, Patrick ; Rondard, Philippe ; Pin, Jean-Philippe. / Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation. In: Nature Communications. 2017 ; Vol. 8, No. 1. pp. 1967.

Bibtex

@article{0e88ab9235014bc3bf33959799694196,
title = "Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation",
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.",
author = "Pauline Scholler and Damien Nevoltris and {de Bundel}, Dimitri and Simon Bossi and David Moreno-Delgado and Xavier Rovira and M{\o}ller, {Thor C} and {El Moustaine}, Driss and Micha{\"e}l Mathieu and Emilie Blanc and Heather McLean and Elodie Dupuis and G{\'e}rard Mathis and Eric Trinquet and Herv{\'e} Daniel and Emmanuel Valjent and Daniel Baty and Patrick Chames and Philippe Rondard and Jean-Philippe Pin",
year = "2017",
month = "12",
day = "6",
doi = "10.1038/s41467-017-01489-1",
language = "English",
volume = "8",
pages = "1967",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation

AU - Scholler, Pauline

AU - Nevoltris, Damien

AU - de Bundel, Dimitri

AU - Bossi, Simon

AU - Moreno-Delgado, David

AU - Rovira, Xavier

AU - Møller, Thor C

AU - El Moustaine, Driss

AU - Mathieu, Michaël

AU - Blanc, Emilie

AU - McLean, Heather

AU - Dupuis, Elodie

AU - Mathis, Gérard

AU - Trinquet, Eric

AU - Daniel, Hervé

AU - Valjent, Emmanuel

AU - Baty, Daniel

AU - Chames, Patrick

AU - Rondard, Philippe

AU - Pin, Jean-Philippe

PY - 2017/12/6

Y1 - 2017/12/6

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-017-01489-1

DO - 10.1038/s41467-017-01489-1

M3 - Journal article

C2 - 29213077

VL - 8

SP - 1967

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -

ID: 200178258