Chapter 8 - Class A GPCR oligomerization: reasons of controversy

Abstract

G protein-coupled receptors (GPCRs) comprise the most studied family of transmembrane proteins. Upon activation by endogenous ligands or agonists, this family of plasma membrane proteins generates intracellular signals with crucial roles in physiology and disease. Over the past 40 years, the number of studies reporting dimerization/oligomerization of GPCRs with relevant pharmacological properties has increased, adding a new dimension to rational drug discovery. Among the GPCR families, the class C GPCRs are well-known dimeric receptors, whereas the concept of homomerization and heteromerization among class A GPCRs is still a matter of intense controversy. Although initial and more recent studies support the monomeric model for class A GPCRs, we have now an extensive amount of data challenging this hypothesis that require special attention. In this chapter, we will discuss the questions underlying this debate with special focus on the pros and cons of the new techniques aiming at the study of the physical interactions of GPCRs.