Methods to Identify the Signature of Trimers Formed by Three G Protein-Coupled Receptors or by Two G Protein-Coupled and One Ionotropic Receptor with Special Emphasis in the Functional Role in the Central Nervous System

Abstract

Whereas ionotropic receptors have been considered as functional units consisting of interacting subunits, G protein-coupled receptors were considered as monomeric cell surface receptors. Experimental evidence from the end of the twentieth century has demonstrated that GPCR may also form dimers, trimers, and even high-order oligomers. Novel techniques (BRET, FRET, SRET) to detect interactions between GPCRs have appeared that led to a substantial advancement in the field, i.e., to identify an ever-increasing number of GPCR homo- and heteroreceptor complexes. A main drawback of these techniques is that they cannot be applied to detection of receptor complexes in brain. Fortunately, novel techniques and novel concepts such as the heteromer signature may be used now to detect GPCR complexes in specific brain regions and in specific neuronal and/or glial cells. Remarkably those techniques make now possible to detect and give insight into the function of receptors formed by even three GPCRs or by two GPCRs and one ionotropic receptor such as the NMDA glutamate receptor. The central nervous system has been the main target for such a revolution in understanding how cell surface receptors participate in neurotransmission and/or regulate cell signaling and fate.