Conformational specificity of opioid receptors is determined by subcellular location irrespective of agonist.

Autor:	Crilly SE; Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, United States.; Department of Pharmacology University of Michigan Medical School, Ann Arbor, United States., Ko W; Department of Pharmacology University of Michigan Medical School, Ann Arbor, United States., Weinberg ZY; Department of Pharmacology University of Michigan Medical School, Ann Arbor, United States., Puthenveedu MA; Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, United States.; Department of Pharmacology University of Michigan Medical School, Ann Arbor, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 May 20; Vol. 10. Date of Electronic Publication: 2021 May 20.
DOI:	10.7554/eLife.67478
Abstrakt:	The prevailing model for the variety in drug responses is that different drugs stabilize distinct active states of their G protein-coupled receptor (GPCR) targets, allowing coupling to different effectors. However, whether the same ligand generates different GPCR active states based on the immediate environment of receptors is not known. Here we address this question using spatially resolved imaging of conformational biosensors that read out distinct active conformations of the δ-opioid receptor (DOR), a physiologically relevant GPCR localized to Golgi and the surface in neuronal cells. We have shown that Golgi and surface pools of DOR both inhibit cAMP, but engage distinct conformational biosensors in response to the same ligand in rat neuroendocrine cells. Further, DOR recruits arrestins on the surface but not on the Golgi. Our results suggest that the local environment determines the active states of receptors for any given drug, allowing GPCRs to couple to different effectors at different subcellular locations. Competing Interests: SC, WK, ZW, MP No competing interests declared (© 2021, Crilly et al.)
Databáze:	MEDLINE
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