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Mol Pharmacol. 2007 Jan;71(1):123-31. Epub 2006 Sep 27.

Interaction of the mu-opioid receptor with synaptophysin influences receptor trafficking and signaling.

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Department of Pharmacology and Toxicology, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.


There is increasing evidence that the signal transduction of opioid receptors is modulated by receptor-associated proteins. In the search for proteins regulating mu-opioid receptor (MOPr) endocytosis, synaptophysin was found to bind to the rat micro-opioid receptor in yeast two-hybrid assay. Coimmunoprecipitation experiments and bioluminescence resonance energy transfer assays confirmed that the micro-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 micro-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 micro-opioid receptor endocytosis. In addition, the synaptophysin-augmented micro-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 micro-opioid receptor trafficking and signaling.

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