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- W4366383399 abstract "Intracellular G protein-coupled receptors (GPCRs) can be activated by permeant ligands, which contributes to agonist selectivity. Opioid receptors (ORs) provide a notable example, where opioid drugs rapidly activate ORs in the Golgi apparatus. Our knowledge on intracellular GPCR function remains incomplete, and it is unknown whether OR signaling in plasma membrane (PM) and Golgi apparatus differs. Here, we assess the recruitment of signal transducers to mu- and delta-ORs in both compartments. We find that Golgi ORs couple to Gαi/o probes and are phosphorylated but, unlike PM receptors, do not recruit β-arrestin or a specific Gα probe. Molecular dynamics simulations with OR–transducer complexes in bilayers mimicking PM or Golgi composition reveal that the lipid environment promotes the location-selective coupling. We then show that delta-ORs in PM and Golgi have distinct effects on transcription and protein phosphorylation. The study reveals that the subcellular location defines the signaling effects of opioid drugs." @default.
- W4366383399 created "2023-04-21" @default.
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- W4366383399 date "2023-04-21" @default.
- W4366383399 modified "2023-10-14" @default.
- W4366383399 title "Subcellular location defines GPCR signal transduction" @default.
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- W4366383399 doi "https://doi.org/10.1126/sciadv.adf6059" @default.
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- W4366383399 hasPublicationYear "2023" @default.
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