Smith, JeffreyPack, Thomas F.Inoue, AsukaLee, ClaudiaZheng, KevinChoi, IssacEiger, Dylan S.Warman, AnmolXiong, XinyuMa, ZhiyuanViswanathan, GayathriLevitan, Ian M.Rochelle, Lauren K.Staus, Dean P.Snyder, Joshua C.Kahsai, Alem W.Caron, Marc G.Rajagopal, Sudarshan2023-12-082021-03-12Smith, Jeffrey, Thomas F. Pack, Asuka Inoue, Claudia Lee, Kevin Zheng, Issac Choi, Dylan S. Eiger et al. "Noncanonical scaffolding of Gαi and β-arrestin by G protein–coupled receptors." Science 371, no. 6534 (2021). DOI: 10.1126/science.aay18330036-80751095-9203https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37377482G 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.en-USMultidisciplinaryJournal Article2023-12-0810.1126/science.aay1833