Driving gonadotrophin hormone receptor signalling: the role of membrane trafficking

: Our understanding of G protein-coupled receptor (GPCR) signalling has significantly evolved over the past decade, whereby signalling not only occurs from the plasma membrane but continues, or is reactivated, following internalisation in to endosomal compartments. The spatial organisation of GPCRs is thus essential to decode dynamic and complex signals, and to activate specific downstream pathways that elicit the appropriate cellular response. For the gonadotrophin hormone receptors, membrane trafficking has been demonstrated to play a significant role in regulating its signal activity that in turn would impact at physiological and even pathophysiological level. Here we will describe the developments in our understanding of the role of 'location' in gonadotrophin hormone receptor signalling, and how these receptors have unveiled fundamental mechanisms of signal regulation likely to be pertinent for other GPCRs. We will also discuss the potential impact of spatially-controlled gonadotrophin hormone receptor signalling in both health and disease, and the therapeutic possibilities this new understanding of these receptors, so key in reproduction, offers.