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

Another way for GPCRs to signal 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 G α proteins in cultured cells using bioluminescent resonance energy transfer. Even though V2Rs do not signal canonically through G α i proteins, they promoted the formation of complexes containing β-arrestin and G α i , and this led to downstream signaling to extracellular signal-regulated kinase protein kinases. Science , this issue p. eaay1833