fig1

Figure 1. Schematic overview of GPCR signaling. (1) GPCR in its inactive state, where the heterotrimeric G protein complex, consisting of a Gα-subunit and a Gβγ-subunit, is still associated and GDP bound; (2) Ligand binding induces the GPCR to undergo a conformational change that initiates G protein coupling. The heterotrimeric G protein complex is activated by GDP exchange for GTP. For a constitutively active GPCR, the G protein constantly couples to the receptor; (3) Subsequently, the subunits dissociate and interact with their corresponding effector proteins, regulating downstream signaling; (4) GPCR signaling is downregulated by G protein-coupled receptor kinase (GRK)-mediated phosphorylation of the C-terminus. Subsequent arrestin binding initiates receptor endocytosis, which can lead to receptor degradation or recycling back to the plasma membrane, as well as endosomal signaling propagation. GPCR: G protein-coupled receptor; AC: adenylyl cyclase; PLCβ: phospholipase C-beta; GRK: G protein-coupled receptor kinase; Arr: arrestin; GDP: guanosine diphosphate; GTP: guanosine triphosphate.