title: A triple arg motif mediates α(2B)-adrenergic receptor interaction with Sec24C/D and export.
abstract: 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 (3R) motif in the third intracellular loop functions as a novel ER export signal for α(2B)-adrenergic receptor (α(2B)-AR). The 3R motif mediates α(2B)-AR interaction with Sec24C/D and modulates ER exit, cell surface transport and function of α(2B)-AR. Furthermore, export function of the 3R motif is independent of its position within α(2B)-AR and can be conferred to CD8 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.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido St, New Orleans, LA 70112, USA.
authors.forename: Chunmin
authors.initials: C
authors.lastname: Dong
authors.forename: Charles D
authors.initials: CD
authors.lastname: Nichols
authors.forename: Jianhui
authors.initials: J
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Nevin A
authors.initials: NA
authors.lastname: Lambert
authors.forename: Guangyu
authors.initials: G
authors.lastname: Wu
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry*; D001665:Binding Sites; D001692:Biological Transport; D016827:CD8 Antigens / Q000737:chemistry; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000737:chemistry*
chemical_list: D016827:CD8 Antigens; D020033:Protein Isoforms; D018341:Receptors, Adrenergic, alpha-2; C530640:SEC24C protein, human; C530641:SEC24D protein, human; D033921:Vesicular Transport Proteins; D001120:Arginine