A Triple Arg Motif Mediates α 2 B ‐Adrenergi c Receptor Interaction with Sec 24 C /D and Export

Recent studies have demonstrated that cargo exit from the endoplasmic reticulum ( ER ) may be directed by ER export motifs recognized by components of the coat protein II (COPII) vesicles. However, little is known about ER export motifs and vesicle targeting of the G protein‐coupled receptor ( GPCR ) superfamily. Here, we have demonstrated that a triple Arg (3 R ) motif in the third intracellular loop functions as a novel ER export signal for α 2 B ‐adrenergic receptor (α 2 B ‐ AR ). The 3 R motif mediates α 2 B ‐ AR interaction with Sec 24 C /D and modulates ER exit, cell surface transport and function of α 2 B ‐ AR . Furthermore, export function of the 3 R motif is independent of its position within α 2 B ‐ AR and can be conferred to CD 8 glycoprotein. These data provide the first evidence implicating that export of GPCRs is controlled by code‐directed interactions with selective components of the COPII transport machinery.