HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 12, 11152-11164, March 25, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/12/11152    most recent M500171200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Law, P.-Y. Articles by Loh, H. H. Search for Related Content PubMed PubMed Citation Articles by Law, P.-Y. Articles by Loh, H. H. Social Bookmarking                      What's this?

Heterodimerization of µ- and -Opioid Receptors Occurs at the Cell Surface Only and Requires Receptor-G Protein Interactions^*

Ping-Yee Law, Laurie J. Erickson-Herbrandson, Qin Q. Zha, Jon Solberg, Ji Chu, Aili Sarre, and Horace H. Loh¶

From the Department of Pharmacology, Medical School, University of Minnesota, Minneapolis, Minnesota 55455-0217

Homo- and heterodimerization of the opioid receptors with functional consequences were reported previously. However, the exact nature of these putative dimers has not been identified. In current studies, the nature of the heterodimers was investigated by producing the phenotypes of the 1:1 heterodimers formed between the constitutively expressed µ-opioid receptor (MOR) and the ponasterone A-induced expression of -opioid receptor (DOR) in EcR293 cells. By examining the trafficking of the cell surface-located MOR and DOR, we determined that these two receptors endocytosed independently. Using cell surface expression-deficient mutants of MOR and DOR, we observed that the corresponding wild types of these receptors could not rescue the cell surface expression of the mutants, whereas the antagonist naloxone could. Furthermore, studies with constitutive or agonist-induced receptor internalization also indicated that MOR and DOR endocytosed independently and could not "drag in" the corresponding wild types or endocytosis-deficient mutants. Additionally, the heterodimer phenotypes could be eliminated by the pretreatment of the EcR293 cells with pertussis toxin and could be modulated by the deletion of the RRITR sequence in the third intracellular loop that is involved in the receptor-G protein interaction and activation. These data suggest that MOR and DOR heterodimerize only at the cell surface and that the oligomers of opioid receptors and heterotrimeric G protein are the bases for the observed MOR-DOR heterodimer phenotypes.

Received for publication, January 6, 2005

^* This research is supported in part by National Institutes of Health Grants DA007339, DA015091, DA016674, and DA011806. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of National Institutes of Health Grant K05 DA00513.

^¶ Recipient of National Institutes of Health Grant K05 DA70544.

To whom all correspondence should be addressed: Dept. of Pharmacology, Medical School, University of Minnesota, 6-120 Jackson Hall, 321 Church St. S. E., Minneapolis, MN 55455-0217; Tel.: 612-626-6497; E-mail: lawxx001{at}umn.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				W. Walwyn, S. John, M. Maga, C. J. Evans, and T. G. Hales {delta} Receptors Are Required for Full Inhibitory Coupling of {micro} Receptors to Voltage-Dependent Ca2+ Channels in Dorsal Root Ganglion Neurons Mol. Pharmacol., July 1, 2009; 76(1): 134 - 143. [Abstract] [Full Text] [PDF]

				X. Ge, H. H. Loh, and P.-Y. Law {micro}-Opioid Receptor Cell Surface Expression Is Regulated by Its Direct Interaction with Ribophorin I Mol. Pharmacol., June 1, 2009; 75(6): 1307 - 1316. [Abstract] [Full Text] [PDF]

				M. Tan, W. M. Walwyn, C. J. Evans, and C.-W. Xie p38 MAPK and {beta}-Arrestin 2 Mediate Functional Interactions between Endogenous {micro}-Opioid and {alpha}2A-Adrenergic Receptors in Neurons J. Biol. Chem., March 6, 2009; 284(10): 6270 - 6281. [Abstract] [Full Text] [PDF]

				F. M. Decaillot, R. Rozenfeld, A. Gupta, and L. A. Devi Cell surface targeting of {micro}-{delta} opioid receptor heterodimers by RTP4 PNAS, October 14, 2008; 105(41): 16045 - 16050. [Abstract] [Full Text] [PDF]

				M. Grant, H. Alturaihi, P. Jaquet, B. Collier, and U. Kumar Cell Growth Inhibition and Functioning of Human Somatostatin Receptor Type 2 Are Modulated by Receptor Heterodimerization Mol. Endocrinol., October 1, 2008; 22(10): 2278 - 2292. [Abstract] [Full Text] [PDF]

				R. C. Y. Choi, J. Simon, K. W. K. Tsim, and E. A. Barnard Constitutive and Agonist-induced Dimerizations of the P2Y1 Receptor: RELATIONSHIP TO INTERNALIZATION AND SCAFFOLDING J. Biol. Chem., April 18, 2008; 283(16): 11050 - 11063. [Abstract] [Full Text] [PDF]

				K. Y. Song, C. K. Hwang, C. S. Kim, H. S. Choi, P.-Y. Law, L.-N. Wei, and H. H. Loh Translational repression of mouse mu opioid receptor expression via leaky scanning Nucleic Acids Res., March 12, 2007; 35(5): 1501 - 1513. [Abstract] [Full Text] [PDF]

				L. A. Snook, G. Milligan, B. L. Kieffer, and D. Massotte {micro}-{delta} Opioid Receptor Functional Interaction: Insight Using Receptor-G Protein Fusions J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 683 - 690. [Abstract] [Full Text] [PDF]

				A. U. Gehret, A. Bajaj, F. Naider, and M. E. Dumont Oligomerization of the Yeast {alpha}-Factor Receptor: IMPLICATIONS FOR DOMINANT NEGATIVE EFFECTS OF MUTANT RECEPTORS J. Biol. Chem., July 28, 2006; 281(30): 20698 - 20714. [Abstract] [Full Text] [PDF]