[Frontiers in Bioscience 14, 3594-3607, January 1, 2009]

Modulation of opioid receptor function by protein-protein interactions

Konstantinos Alfaras-Melainis1,2, Ivone Gomes1, Raphael Rozenfeld1, Venetia Zachariou2, Lakshmi Devi1

1Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA, 2Department of Pharmacology, University of Crete, Heraklion, Crete, Greece

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Proteins involved in biogenesis/trafficking of opioid receptors
4. Proteins that modulate opioid receptor signaling
4.1. Regulators of G-protein signaling
4.2. G-protein-coupled receptor kinases
4.3. beta-arrestins
4.4. Other proteins
5. Proteins involved in endocytosis and degradation
5.1. Protein interactions that modulate receptor endocytosis
5.2. Proteins that modulate receptor degradation
6. Interactions with other GPCRs that modulate receptor function
7. Summary and Perspectives
8. Acknowledgements
9.References

1. ABSTRACT

Opioid receptors, MORP, DORP and KORP, belong to the family A of G protein coupled receptors (GPCR), and have been found to modulate a large number of physiological functions, including mood, stress, appetite, nociception and immune responses. Exogenously applied opioid alkaloids produce analgesia, hedonia and addiction. Addiction is linked to alterations in function and responsiveness of all three opioid receptors in the brain. Over the last few years, a large number of studies identified protein-protein interactions that play an essential role in opioid receptor function and responsiveness. Here, we summarize interactions shown to affect receptor biogenesis and trafficking, as well as those affecting signal transduction events following receptor activation. This article also examines protein interactions modulating the rate of receptor endocytosis and degradation, events that play a major role in opiate analgesia. Like several other GPCRs, opioid receptors may form homo or heterodimers. The last part of this review summarizes recent knowledge on proteins known to affect opioid receptor dimerization.