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

J. Biol. Chem., Vol. 281, Issue 12, 7983-7993, March 24, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/12/7983    most recent M509805200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, C. Articles by Liu-Chen, L.-Y. Search for Related Content PubMed PubMed Citation Articles by Chen, C. Articles by Liu-Chen, L.-Y. Social Bookmarking                      What's this?

GEC1 Interacts with the Opioid Receptor and Enhances Expression of the Receptor^*

From the Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania 19140

We identified a truncated form (38–117) of GEC1 that interacts with the C-tail of the human opioid receptor (hKOR) by yeast two-hybrid screening. GEC1-(38–117) did not interact with the C-tail of the µ or opioid receptors. GEC1, a 117-amino acid protein (Pellerin, I., Vuillermoz, C., Jouvenot, M., Ordener, C., Royez, M., and Adessi, G. L. (1993) Mol. Cell Endocrinol. 90, R17–R21), is highly homologous to GABARAP, GATE-16, and Apg8/aut7, all members of the microtubule associated protein (MAP) family. In pull-down assays, GST-GEC1 interacted directly with the hKOR C-tail, full-length hKOR, and tubulin. When expressed in Chinese hamster ovary (CHO) cells, GEC1 co-immunoprecipitated with FLAG-hKOR. Expression of GEC1 greatly increased total and cell-surface KOR but not µ or opioid receptors. GEC1 expression slightly reduced U50,488H-promoted down-regulation, without affecting ligand binding affinity, receptor-G protein coupling, or U50,488H-induced desensitization and internalization. HA-GEC1 expressed in CHO cells was localized in the Golgi apparatus and endoplasmic reticulum (ER). When cells were pulsed with [³⁵S]Met/Cys, GEC1 expression enhanced the level of the mature form (55-kDa band) of FLAG-hKOR at 4, 8, and 22 h after pulse without affecting the precursors (39- and 45-kDa bands), indicating that GEC1 facilitates trafficking of FLAG-hKOR from the ER/Golgi to plasma membranes. GEC1 interacted with N-ethylmaleimide-sensitive factor (NSF) in pull-down assays and co-immunoprecipitated with NSF in rat brain extracts. The interaction with NSF may contribute to GEC1 effects. This is the first report on biological functions of GEC1 and the first demonstration that a GPCR interacts with a protein of the MAP family. The interaction is important for trafficking of the receptor in the biosynthesis pathway.

Received for publication, September 7, 2005 , and in revised form, January 17, 2006.

^* This work was supported by National Institutes of Health Grants DA17302 and DA04745. 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.

¹ To whom correspondence should be addressed: Dept. of Pharmacology, Temple University School of Medicine, 3420 N. Broad St., Philadelphia, PA 19140. Tel.: 215-707-4188; Fax: 215-707-7068; E-mail: lliuche{at}temple.edu.

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

This article has been cited by other articles:

				S. Slavikova, S. Ufaz, T. Avin-Wittenberg, H. Levanony, and G. Galili An autophagy-associated Atg8 protein is involved in the responses of Arabidopsis seedlings to hormonal controls and abiotic stresses J. Exp. Bot., October 3, 2008; (2008) ern244v1. [Abstract] [Full Text] [PDF]

				J. L. Cook, R. N. Re, D. L. deHaro, J. M. Abadie, M. Peters, and J. Alam The Trafficking Protein GABARAP Binds to and Enhances Plasma Membrane Expression and Function of the Angiotensin II Type 1 Receptor Circ. Res., June 20, 2008; 102(12): 1539 - 1547. [Abstract] [Full Text] [PDF]

				J.-G. Li, D. S. Haines, and L.-Y. Liu-Chen Agonist-Promoted Lys63-Linked Polyubiquitination of the Human {kappa}-Opioid Receptor Is Involved in Receptor Down-Regulation Mol. Pharmacol., April 1, 2008; 73(4): 1319 - 1330. [Abstract] [Full Text] [PDF]

				Y. Wang, Y. Chen, W. Xu, D. Y.W. Lee, Z. Ma, S. M. Rawls, A. Cowan, and L.-Y. Liu-Chen 2-Methoxymethyl-Salvinorin B Is a Potent {kappa} Opioid Receptor Agonist with Longer Lasting Action in Vivo Than Salvinorin A J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1073 - 1083. [Abstract] [Full Text] [PDF]

				Y. Chen, C. Chen, Y. Wang, and L.-Y. Liu-Chen Ligands Regulate Cell Surface Level of the Human {kappa} Opioid Receptor by Activation-Induced Down-Regulation and Pharmacological Chaperone-Mediated Enhancement: Differential Effects of Nonpeptide and Peptide Agonists J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 765 - 775. [Abstract] [Full Text] [PDF]