G-protein coupled receptors (GPCRs) are a large family of cell surface receptors important for activating cellular responses. They are activated by many types of signals like light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters and are involved in a wide range of diseases which have made them important drug targets. Receptor activity-modifying proteins (RAMPs) form complexes with the GPCRs and may regulate their cellular trafficking and pharmacology.

In a publication in Science Advances the GPCR-RAMP interactome was investigated by coexpressing more than 200 dual epitope-tagged (DuET) GPCRs, representing all GPCR subfamilies, with each of three different RAMPS. The GPCR-RAMP pairs were then screened using multiplexed suspension bead array (SBA) immunoassays. Using this approach more than half of the GPCRs were shown to interact with at least one RAMP and most of the RAMP interacting GPCRs formed complexes with two or all three RAMPs.

The SBA assay was further used to detect endogenous GPCR-RAMP interactions in solubilized membranes from three different cell lines. This resulted in the identification of 23 GPCRs that formed complexes with at least one RAMP, and most of these specific GPCR-RAMP interacting pairs were previously unreported. Elucidating the GPCR-RAMP interactome helps in characterization of RAMP-interacting GPCRs and may aid in the design of selective therapeutics targeting these complexes.

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