Noncanonical scaffolding of Gαi and β-arrestin by G protein–coupled receptors

Abstract

G protein–coupled receptors (GPCRs) normally transmit signals by coupling to heterotrimeric guanine nucleotide–binding proteins (G proteins) or by binding β-arrestin proteins. Smith et al. provide evidence for another mechanism, an approximate combination of the two. They monitored the interaction of vasopressin type 2 receptors (V2Rs) and Gα proteins in cultured cells using bioluminescent resonance energy transfer. Even though V2Rs do not signal canonically through Gαi proteins, they promoted the formation of complexes containing β-arrestin and Gαi, and this led to downstream signaling to extracellular signal-regulated kinase protein kinases.