Di/Oligomerization of GPCRs-Mechanisms and Functional Significance

Initially considered as strict and rigid monomers, GPCRs have shown an ever-increasing flexibility in the number of intermolecular interactions they can participate in. Few rules can be applied to all members of this receptor superfamily, as the functional roles of resulting dimers or oligomers vary widely from biosynthesis, functional complementation, enhancement and control of signaling, positive and negative cooperativity, signal desensitization, membrane trafficking, and pharmacological diversity, among others. Receptor dimerization/oligomerization is a challenging phenomenon to disentangle even in vitro and thus in vivo evidence for its functional significance requires employment of a variety of cutting-edge techniques. Nevertheless, the evidence for GPCR di/oligomerization at the physiological level is mounting and has begun to shed light on an intricate network of interactions that challenge the previous knowledge on how this family of receptors function. Here, we summarize the evidence for GPCR di/oligomerization in living organisms with a particular focus of their involvement in health and disease.