Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein

Many structural determinants for G protein-coupled receptor (GPCR) function s have been defined, but little is known concerning the regulation of their transport from the endoplasmic reticulum (ER) to the cell surface. Here we show that a carboxy-terminal hydrophobic motif, FxxxFxxxF, which is highly conserved among GPCRs, functions independently as an ER-export signal for the dopamine D1 receptor. A newly identified ER-membrane-associated protein , DRiP78, binds to this motif. Overexpression or sequestration of DRiP78 le ads to retention of D1 receptors in the ER, reduced ligand binding, and a s lowdown in the kinetics of receptor glycosylation. Our results indicate tha t DRiP78 may regulate the transport of a GPCR by binding to a specific ER-e xport signal.