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

Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13672-6. doi: 10.1073/pnas.0403854101. Epub 2004 Sep 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists
  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Endocytosis
  • Epithelium / metabolism
  • Gene Expression Regulation*
  • Humans
  • Mice
  • Microscopy, Confocal
  • Protein Binding
  • Protein Transport
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Adrenergic, beta-2 / genetics*
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Receptors, Odorant / agonists
  • Receptors, Odorant / genetics*
  • Receptors, Odorant / metabolism*


  • Adrenergic beta-2 Receptor Agonists
  • RNA, Messenger
  • Receptors, Adrenergic, beta-2
  • Receptors, Odorant