G protein-coupled receptors (GPCRs) mediate a diverse range of physiological functions via activation of complex signaling systems. Organization of GPCRs in to dimers and oligomers provides a mechanism for both signal diversity and specificity in cellular responses, yet our understanding of the physiological significance of dimerization, particularly homodimerization, has not been forthcoming. This chapter will describe how we have investigated the physiological importance of GPCR homodimerization, using the luteinizing hormone/chorionic gonadotropin receptor as a model GPCR. Using transactivation as a mode of assessing receptor dimerization, we describe our cellular system and functional assays for assessment of transactivation in vitro and detail our strategy for generating a mouse model to assess GPCR transactivation in vivo.
