BRET-based effector membrane translocation assay monitors GPCR-promoted and endocytosis-mediated G q activation at early endosomes

著者: Shane C. Wright, Viktoriya Lukasheva, Christian Le Gouill, Hiroyuki Kobayashi, Billy Breton, Samuel Mailhot-Larouche, Élodie Blondel-Tepaz, Nichelle Antunes Vieira, Cláudio M. Costa-Neto, Madeleine Héroux, Nevin A. Lambert, Lucas T. Parreiras‐e‐Silva, Michel Bouvier - Proceedings of the National Academy of Sciences, PNAS 2021 被引用: 66

Significance G protein–coupled receptors (GPCRs) have been proposed to signal in multiple compartments within the cell, a phenomenon that could have important implications for our understanding of receptor pharmacology and disease treatment. However, directly measuring G protein activity in subcellular compartments remains a challenge, and the mechanism underlying their translocation and activation remains elusive. Using a biosensor that specifically measures the presence of GTP-loaded G q/11 at endosomes, our findings reveal the mechanism underlying G q trafficking and signaling in the endosome and provide a powerful tool to directly monitor G protein movement and activation in subcellular compartments.