Regulation of anterograde transport of alpha2-adrenergic receptors by the N termini at multiple intracellular compartments.
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.
Dong
Chunmin
C
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, USA.
Wu
Guangyu
G
D000595:Amino Acid Sequence; D019390:Arrestins / Q000378:metabolism; D020126:Brefeldin A / Q000494:pharmacology; D002451:Cell Compartmentation; D002460:Cell Line; D019281:Dimerization; D034281:Dynamins / Q000378:metabolism; D006801:Humans; D021381:Protein Transport; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
D019390:Arrestins; D018341:Receptors, Adrenergic, alpha-2; C082333:arrestin3; D020126:Brefeldin A; D020696:rab5 GTP-Binding Proteins; D034281:Dynamins