Olfactory receptor surface expression is driven by association with the beta2-adrenergic receptor.

Autor: Hague C; Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA. chague@emory.edu, Uberti MA, Chen Z, Bush CF, Jones SV, Ressler KJ, Hall RA, Minneman KP
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2004 Sep 14; Vol. 101 (37), pp. 13672-6. Date of Electronic Publication: 2004 Sep 03.
DOI: 10.1073/pnas.0403854101
Abstrakt: 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.
Databáze: MEDLINE