Chapter 12:Crosstalk Between Receptors: Challenges of Distinguishing Upstream from Downstream Mechanisms

G protein-coupled receptors (GPCRs) constitute one of the largest families of cell surface proteins that initiate intracellular signalling in response to a diverse array of ligands and play a vital role in cell–cell communication as well as smell, taste and vision. Considerable evidence suggests that GPCRs form homomeric and heteromeric complexes that can lead to novel pharmacological properties. Although receptor coexpression can lead to signal integration and crosstalk, the underlying molecular mechanisms are still not well understood. In this chapter we discuss the various signalling possibilities that result from receptor coexpression, as well as novel approaches that combine the power of protein complementation and resonance energy transfer to allow us to study individual components of a GPCR signalling unit.