Regulation of anterograde transport of α2-adrenergic receptors by the N termini at multiple intracellular compartments

Abstract

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 α2-adrenergic receptors (α2-ARs) in the anterograde transport from the endoplasmic reticulum (ER) through the Golgi to the cell surface. The N-terminal-truncated α2B-AR mutant is completely unable to target to the cell surface. A single Met-6 residue is essential for the export of α2B-AR from the ER, likely through modulating correct α2B-AR folding in the ER. The Tyr-Ser motif, highly conserved in the membrane-proximal N termini of all α2-AR subtypes, is required for the exit of α2A-AR and α2B-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. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.