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First published on September 27, 2006; DOI: 10.1124/mol.106.026062


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Received for publication May 3, 2006.
Revised September 27, 2006.
Accepted for publication September 27, 2006.

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

Ying-Jian Liang 1, Dai-Fei Wu 1, Li-Quan Yang 1, Volker Hollt 1, Thomas Koch 1*

1 Department of Pharmacology and Toxicology, Otto-von-Guericke University

* Address correspondence to: E-mail: thomas.koch{at}medizin.uni-magdeburg.de

Abstract

There is increasing evidence that the signal transduction of opioid receptors is modulated by receptor-associated proteins. In search of proteins regulating µ-opioid receptor (MOPr) endocytosis, synaptophysin was found to bind to the rat µ-opioid receptor in yeast two-hybrid assay. Co-immunoprecipitation experiment and bioluminescence resonance energy transfer (BRET) assay confirmed that the µ-opioid receptor constitutively interacts with synaptophysin in human embryonic kidney (HEK) 293 cells over-expressing MOPr and synaptophysin. Here we show that over-expression 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 over-expression 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 an attenuated agonist-induced receptor desensitization and a faster receptor resensitization. Taken together, our findings strongly suggest that synaptophysin play an important role in the regulation of µ-opioid receptor trafficking and signaling.


Key words: Desensitization/uncoupling, Sequestration/Internalization, Recycling


This article has been cited by other articles:


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D.-F. Wu, T. Koch, Y.-J. Liang, R. Stumm, S. Schulz, H. Schroder, and V. Hollt
Membrane Glycoprotein M6a Interacts with the {micro}-Opioid Receptor and Facilitates Receptor Endocytosis and Recycling
J. Biol. Chem., July 27, 2007; 282(30): 22239 - 22247.
[Abstract] [Full Text] [PDF]




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