Noncanonical scaffolding of G{alpha}i and {beta}-arrestin by G protein-coupled receptors

Heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) are common drug targets and canonically couple to specific Gα protein subtypes and β-arrestin adaptor proteins. G protein–mediated signaling and β-arrestin–mediated signaling have been considered separable. We show here that GPCRs promote a direct interaction between Gαi protein subtype family members and β-arrestins regardless of their canonical Gα protein subtype coupling. Gαi:β-arrestin complexes bound extracellular signal–regulated kinase (ERK), and their disruption impaired both ERK activation and cell migration, which is consistent with β-arrestins requiring a functional interaction with Gαi for certain signaling events. These results introduce a GPCR signaling mechanism distinct from canonical G protein activation in which GPCRs cause the formation of Gαi:β-arrestin signaling complexes.

Source: ScienceNOW - March 11, 2021 Category: Science Authors: Smith, J. S., Pack, T. F., Inoue, A., Lee, C., Zheng, K., Choi, I., Eiger, D. S., Warman, A., Xiong, X., Ma, Z., Viswanathan, G., Levitan, I. M., Rochelle, L. K., Staus, D. P., Snyder, J. C., Kahsai, A. W., Caron, M. G., Rajagopal, S. Tags: Cell Biology, Online Only r-articles Source Type: news