G protein-coupled receptors (GPCRs) represent the largest family of cell surface proteins. Agonist binding to GPCRs activates G proteins regulating many cellular effectors. Classically, G protein activation occurs at the plasma membrane and is rapidly terminated by β-arrestin recruitment to the activated GPCRs, promoting G protein uncoupling from receptor, GPCR internalisation and signalling arrest. 

However, recent studies revealed that upon internalisation, some GPCRs continue to activate G proteins from internal compartments leading to sustained production of second messengers far from the plasma membrane. This different spatiotemporal signalling profile allows distinct cellular functions from the ones occurring at the plasma membrane that can be exploited in the near future to design new pharmacological approaches. My research programme aims to tackle important questions underlying this novel signalling mode.