RT Journal Article SR Electronic T1 Interaction of the μ-Opioid Receptor with Synaptophysin Influences Receptor Trafficking and Signaling JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 123 OP 131 DO 10.1124/mol.106.026062 VO 71 IS 1 A1 Ying-Jian Liang A1 Dai-Fei Wu A1 Li-Quan Yang A1 Volker Höllt A1 Thomas Koch YR 2007 UL http://molpharm.aspetjournals.org/content/71/1/123.abstract AB There is increasing evidence that the signal transduction of opioid receptors is modulated by receptor-associated proteins. In the search for proteins regulating μ-opioid receptor (MOPr) endocytosis, synaptophysin was found to bind to the rat μ-opioid receptor in yeast two-hybrid assay. Coimmunoprecipitation experiments and bioluminescence resonance energy transfer assays confirmed that the μ-opioid receptor constitutively interacts with synaptophysin in human embryonic kidney 293 cells overexpressing MOPr and synaptophysin. In this study, we show that overexpression of synaptophysin enhances the μ-opioid receptor endocytosis. One explanation for the observed effects is that synaptophysin recruits dynamin to the plasma membrane, facilitating fission of clathrin-coated vesicles. This suggestion is supported by our finding that overexpression of a synaptophysin truncation mutant, which breaks the interaction between synaptophysin and dynamin, prevents agonist-mediated μ-opioid receptor endocytosis. In addition, the synaptophysin-augmented μ-opioid receptor trafficking leads to attenuated agonist-induced receptor desensitization and faster receptor resensitization. Taken together, our findings strongly suggest that synaptophysin plays an important role in the regulation of μ-opioid receptor trafficking and signaling. The American Society for Pharmacology and Experimental Therapeutics