β-arrestins and endocrine-related GPCRs
Résumé
G protein-coupled receptors (GPCRs) allow target cells to respond to a wide array of hormones. Mounting evidences point to GPCRs being functionally coupled to multiple transduction mechanisms, some of them not involving heterotrimeric G proteins. Among these emerging mechanisms, it has been well established that β-arrestins recruited to active GPCRs control not only their desensitization and internalization, but also assemble and activate signaling modules in different intracellular compartments. Importantly, β-arrestin-dependent transduction applies to most GPCRs, including those involved in endocrine mechanisms. This concept, in conjunction with remarkable advances made over the last decade in structural biology and biophysics of GPCRs, supports the notion of ligand-selective signaling also known as pharmacological bias. In this chapter, we review the role of β-arrestin recruitment in the signaling and trafficking of endocrine-related GPCRs. We also focus on biased ligands capable of selectively activating intracellular pathways downstream of endocrine-related GPCRs and discuss their potential therapeutic applications.