TY - JOUR TI - Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs AU - Avet, Charlotte AU - Mancini, Arturo AU - Breton, Billy AU - Le Gouill, Christian AU - Hauser, Alexander S AU - Normand, Claire AU - Kobayashi, Hiroyuki AU - Gross, Florence AU - Hogue, Mireille AU - Lukasheva, Viktoriya AU - St-Onge, Stéphane AU - Carrier, Marilyn AU - Héroux, Madeleine AU - Morissette, Sandra AU - Fauman, Eric B AU - Fortin, Jean-Philippe AU - Schann, Stephan AU - Leroy, Xavier AU - Gloriam, David E AU - Bouvier, Michel A2 - Weis, William I A2 - Aldrich, Richard W A2 - Sunahara, Roger VL - 11 PY - 2022 DA - 2022/03/18 SP - e74101 C1 - eLife 2022;11:e74101 DO - 10.7554/eLife.74101 UR - https://doi.org/10.7554/eLife.74101 AB - The recognition that individual GPCRs can activate multiple signaling pathways has raised the possibility of developing drugs selectively targeting therapeutically relevant ones. This requires tools to determine which G proteins and βarrestins are activated by a given receptor. Here, we present a set of BRET sensors monitoring the activation of the 12 G protein subtypes based on the translocation of their effectors to the plasma membrane (EMTA). Unlike most of the existing detection systems, EMTA does not require modification of receptors or G proteins (except for Gs). EMTA was found to be suitable for the detection of constitutive activity, inverse agonism, biased signaling and polypharmacology. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity. Overall, this work describes unique resources for studying the complexities underlying GPCR signaling and pharmacology. KW - g protein-coupled receptor KW - enhanced bystander bioluminescence resonance energy transfer KW - effector membrane translocation assay KW - biosensor KW - G protein activation KW - high-throughput assay JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -