Agonist-selective signaling is determined by the receptor location within the membrane domains

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 27; pp. 9421 - 9426
• Main Authors: Zheng, Hui, Chu, Ji, Qiu, Yu, Loh, Horace H, Law, Ping-Yee
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 08.07.2008; National Acad Sciences
• Subjects: adenylate cyclase; Agonists; Animals; Antibodies; Arrestins - metabolism; beta-Arrestins; beta-Cyclodextrins - pharmacology; Binding sites; Biological Sciences; Cell Line; Cell membranes; Cholesterols; Colforsin - pharmacology; dissociation; etorphine; Etorphine - pharmacology; Gene Deletion; GTP-Binding Protein alpha Subunit, Gi2 - metabolism; guanosine triphosphate; HEK293 cells; Humans; hydrolysis; Lipids; Male; Membrane Microdomains - drug effects; Membrane Microdomains - metabolism; Membranes; Mice; Mice, Inbred C57BL; Microscopy, Confocal; mitogen-activated protein kinase; Morphine; Morphine - pharmacology; Mutant Proteins - metabolism; Phosphorylation; Protein Binding - drug effects; Protein Transport - drug effects; Proteins; Rafts; Receptors; Receptors, Opioid, mu - agonists; Signal transduction; Signal Transduction - drug effects; Translocation

The basis for agonist-selective signaling was investigated by using the μ-opioid receptor (MOR) as a model. In the absence of agonist, MOR located within the lipid raft domains, whereas etorphine, but not morphine, induced the translocation of MOR from lipid raft to nonraft domains, similar to the a...