Cannabinoid receptor CB1 and CB2 interacting proteins: Techniques, progress and perspectives.

Abstract Cannabinoid receptors 1 and 2 (CB1 and CB2) are implicated in a range of physiological processes and have gained attention as promising therapeutic targets for a number of diseases. Protein-protein interactions play an integral role in modulating G protein-coupled receptor (GPCR) expression, subcellular distribution and signaling, and the identification and characterization of these will not only improve our understanding of GPCR function and biology, but may provide a novel avenue for therapeutic intervention. A variety of techniques are currently being used to investigate GPCR protein-protein interactions, including Forster/fluorescence and bioluminescence resonance energy transfer (FRET and BRET), proximity ligation assay (PLA), and bimolecular fluorescence complementation (BiFC). However, the reliable application of these methodologies is dependent on the use of appropriate controls and the consideration of the physiological context. Though not as extensively characterized as some other GPCRs, the investigation of CB1 and CB2 interacting proteins is a growing area of interest, and a range of interacting partners have been identified to date. This review summarizes the current state of the literature regarding the cannabinoid receptor interactome, provides commentary on the methodologies and techniques utilized, and discusses future perspectives.