Techniques for the study of GPCR heteromerization in living cells and animal models

G protein-coupled receptors (GPCRs) have traditionally been considered to exist and function as monomeric structural units—hypothesis that is further supported by recent findings based on both membrane protein reconstitution systems and X-ray crystal structures. Nevertheless, a vast body of experimental data obtained over the past decade provides plausible evidence to support a model whereby close molecular proximity between two or more GPCRs at the plasma membrane affects receptor pharmacology and its intracellular signaling properties. Most of these findings, however, have been achieved in cultured cells, and hence the capacity of GPCRs to form dimeric or oligomeric complexes in whole animal models remains largely unknown. This chapter describes experimental approaches in vitro and in vivo that can be used to study GPCR dimerization/oligomerization, with special emphasis on heteromeric receptor complexes.