Afficher la couverture 'Nanobody-based sensors reveal a high proportion of mGlu heterodimers in the brain | Meng, Jiyong' en grand format
/5

0 avis

Nanobody-based sensors reveal a high proportion of mGlu heterodimers in the brain

Archive ouverte

Meng, Jiyong | Xu, Chanjuan | Lafon, Pierre-André | Roux, Salomé | Mathieu, Michaël | Zhou, Rui | Scholler, Pauline | Blanc, Emilie | Becker, Jérôme | Le Merrer, Julie | González-Maeso, Javier | Chames, Patrick | Liu, Jianfeng | Pin, Jean-Philippe | Rondard, Philippe

Edité par CCSD ; Nature Publishing Group -

International audience. Membrane proteins, including ion channels, receptors and transporters, are often composed of multiple subunits and can form large complexes. Their specific composition in native tissues is difficult to determine and remains largely unknown. In this study, we developed a method for determining the subunit composition of endogenous cell surface protein complexes from isolated native tissues. Our method relies on nanobody-based sensors, which enable proximity detection between subunits in time-resolved Förster resonance energy transfer (FRET) measurements. Additionally, given conformation-specific nanobodies, the activation of these complexes can be recorded in native brain tissue. Applied to the metabotropic glutamate receptors in different brain regions, this approach revealed the clear existence of functional metabotropic glutamate (mGlu)2-mGlu4 heterodimers in addition to mGlu2 and mGlu4 homodimers. Strikingly, the mGlu4 subunits appear to be mainly heterodimers in the brain. Overall, these versatile biosensors can determine the presence and activity of endogenous membrane proteins in native tissues with high fidelity and convenience.

Suggestions

Du même auteur

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

Archive ouverte | Scholler, Pauline | CCSD

International audience. 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 prog...

Chronic potentiation of metabotropic glutamate receptor 2 with a nanobody accelerates amyloidogenesis in Alzheimer’s disease.

Archive ouverte | Lafon, Pierre-André | CCSD

International audience. Immunotherapy of Alzheimer's disease (AD) is a promising approach to reduce the accumulation of amyloid-beta (Aβ), a critical event in the onset of the disease. Targeting the group II metabot...

Allosteric ligands control the activation of a class C GPCR heterodimer by acting at the transmembrane interface

Archive ouverte | Liu, Lei | CCSD

International audience. G protein-coupled receptors (GPCRs) are among the most promising drug targets. They often form homo- and heterodimers with allosteric cross-talk between receptor entities, which contributes t...

Chargement des enrichissements...