In vivo mapping of a GPCR interactome using knockin mice.

In vivo mapping of a GPCR interactome using knockin mice.

Publication date: May 26, 2020

With over 30% of current medications targeting this family of proteins, G-protein-coupled receptors (GPCRs) remain invaluable therapeutic targets. However, due to their unique physicochemical properties, their low abundance, and the lack of highly specific antibodies, GPCRs are still challenging to study in vivo. To overcome these limitations, we combined here transgenic mouse models and proteomic analyses in order to resolve the interactome of the ?-opioid receptor (DOPr) in its native in vivo environment. Given its analgesic properties and milder undesired effects than most clinically prescribed opioids, DOPr is a promising alternative therapeutic target for chronic pain management. However, the molecular and cellular mechanisms regulating its signaling and trafficking remain poorly characterized. We thus performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses on brain homogenates of our newly generated knockin mouse expressing a FLAG-tagged version of DOPr and revealed several endogenous DOPr interactors involved in protein folding, trafficking, and signal transduction. The interactions with a few identified partners such as VPS41, ARF6, Rabaptin-5, and Rab10 were validated. We report an approach to characterize in vivo interacting proteins of GPCRs, the largest family of membrane receptors with crucial implications in virtually all physiological systems.

Concepts Keywords
Analgesic Physiological systems
Antibodies MS
Brain Pain management
Chronic Pain Branches of biology
Endogenous Molecular biology
G Protein Signal transduction
GPCR G protein-coupled receptors
Interactome Biochemistry
Liquid Chromatography Bioinformatics
Membrane Interactome
Mice Opioid receptor
Opioid Receptor Antibodies
Pain Management
Signal Transduction
Tandem Mass Spectrometry


Type Source Name
disease MESH chronic pain

Original Article

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