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Originally published In Press as doi:10.1074/jbc.M605734200 on October 12, 2006

J. Biol. Chem., Vol. 281, Issue 50, 38543-38554, December 15, 2006
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Regulation of Anterograde Transport of {alpha}2-Adrenergic Receptors by the N Termini at Multiple Intracellular Compartments*

Chunmin Dong and Guangyu Wu1

From the Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112

The studies on the intrinsic structural determinants for export trafficking of G protein-coupled receptors (GPCRs) have been mainly focused on the C termini of the receptors. In this report we determined the role of the extracellular N termini of {alpha}2-adrenergic receptors ({alpha}2-ARs) in the anterograde transport from the endoplasmic reticulum (ER) through the Golgi to the cell surface. The N-terminal-truncated {alpha}2B-AR mutant is completely unable to target to the cell surface. A single Met-6 residue is essential for the export of {alpha}2B-AR from the ER, likely through modulating correct {alpha}2B-AR folding in the ER. The Tyr-Ser motif, highly conserved in the membrane-proximal N termini of all {alpha}2-AR subtypes, is required for the exit of {alpha}2A-AR and {alpha}2B-AR from the Golgi apparatus, thus representing a novel Tyr-based motif modulating GPCR transport at the Golgi level. These data provide the first evidence indicating an essential role of the N termini of GPCRs in the export from distinct intracellular compartments along the secretory pathway.


Received for publication, June 15, 2006 , and in revised form, September 5, 2006.

* This work was supported by National Institutes of Health Grants R01GM076167 (to G. W.) and P20RR018766 (to G. W. and Stephen M. Lanier) and by the American Heart Association, Southeast affiliate (to C. D.). 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 and Experimental Therapeutics, LA State University Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112. Tel.: 504-568-2236; Fax: 504-568-2361; E-mail: gwu{at}lsuhsc.edu.


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