Regulation of GPCR signal networks via membrane trafficking.

G-protein-coupled receptors (GPCRs) are a superfamily of cell surface signaling proteins that act as central molecular activators and integrators in all endocrine systems. Membrane trafficking of GPCRs is a fundamental process in shaping extensive signaling networks activated by these receptors. Mounting evidence has identified an increasingly complex network of pathways and protein interactions that a GPCR can traverse and associate with, indicating a multi-level system of regulation. This review will discuss the recent developments in how GPCRs are trafficked to the cell surface as newly synthesized receptors, their recruitment to the clathrin-mediated pathway for endocytosis, and their sorting to subsequent divergent post-endocytic fates, focusing primarily on hormone-activated GPCRs. Current models depicting the classic roles membrane trafficking plays in GPCR signaling have evolved to a highly regulated and complex system than previously appreciated. These developments impart key mechanistic information on how spatial and temporal aspects of GPCR signaling may be integrated and could provide pathway-specific targets to be exploited for therapeutic intervention.

Past, present and future of vasopressin and oxytocin receptor oligomers, prototypical GPCR models to study dimerization processes.

The G protein-coupled receptors (GPCRs) play a major role in the regulation of physiological function. The emergence of the concept of GPCR oligomerization deeply modifies our understanding of their functioning. Much more than a simple association leading to an independent functioning, the GPCR oligomerization affects various steps such as membrane targeting of the receptors, binding of ligands, coupling to the intracellular pathways and internalization. Although significant advances have been performed in proving the existence of GPCR oligomers, its physiological impact remains to be established. Vasopressin and oxytocin receptors have constituted interesting experimental models in oligomer analysis. Because of the pharmacological tools available regarding these receptors and their expression at a high level in various tissues they can constitute very promising models to study the consequences of oligomerization in physiology.