Olfactory receptor surface expression is driven by association with the beta2-adrenergic receptor.
Olfactory receptors (ORs) comprise more than half of the large class I G protein-coupled receptor (GPCR) superfamily. Although cloned over a decade ago, little is known about their properties because wild-type ORs do not efficiently reach the cell surface following heterologous expression. Receptor-receptor interactions strongly influence surface trafficking of other GPCRs, and we examined whether a similar mechanism might be involved in OR surface expression. Olfactory neurons are known to express beta-adrenergic receptors (ARs), and we found that coexpression with beta(2)-ARs, but not any other AR subtypes, dramatically increased mouse 71 (M71) OR surface expression in human embryonic kidney 293 cells. A persistent physical interaction between M71 ORs and beta(2)-ARs was shown by coimmunoprecipitation and by cointernalization of the two receptors in response to their specific ligands. Also, coexpression of wild-type M71 ORs with beta(2)-ARs resulted in cAMP responses to the M71 ligand acetophenone. Finally, in situ hybridization studies showed extensive colocalization of M71 OR and beta(2)-AR expression in mouse olfactory epithelium. These data demonstrate the successful heterologous surface expression of a functional wild-type OR and reveal that persistent physical association with other GPCRs can control OR surface expression.
Hague
Chris
C
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA. chague@emory.edu
Uberti
Michelle A
MA
Chen
Zhongjian
Z
Bush
Cristina F
CF
Jones
Seth V
SV
Ressler
Kerry J
KJ
Hall
Randy A
RA
Minneman
Kenneth P
KP
D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D011485:Protein Binding; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism*; D018035:Receptors, Odorant / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*
D058666:Adrenergic beta-2 Receptor Agonists; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D018035:Receptors, Odorant