title: Specificity of olfactory receptor interactions with other G protein-coupled receptors.
abstract: Studies on olfactory receptor (OR) pharmacology have been hindered by the poor plasma membrane localization of most ORs in heterologous cells. We previously reported that association with the beta(2)-adrenergic receptor (beta(2)-AR) facilitates functional expression of the OR M71 at the plasma membrane of HEK-293 cells. In the present study, we examined the specificity of M71 interactions with other G protein-coupled receptors (GPCRs). M71 was co-expressed in HEK-293 cells with 42 distinct GPCRs, and the vast majority of these receptors had no significant effect on M71 surface expression. However, co-expression with three subtypes of purinergic receptor (P2Y(1)R, P2Y(2)R, and A(2A)R) resulted in markedly enhanced plasma membrane localization of M71. Agonist stimulation of M71 co-expressed with P2Y(1)R and P2Y(2)R activated the mitogen-activated protein kinase pathway via coupling of M71 to Galpha(o). We also examined the ability of beta(2)-AR, P2Y(1)R, P2Y(2)R, and A(2A)Rto interact with and regulate ORs beyond M71. We found that co-expression of beta(2)-AR or the purinergic receptors enhanced the surface expression for an M71 subfamily member but not for several other ORs from different subfamilies. In addition, through chimeric receptor studies, we determined that the second transmembrane domain of beta(2)-AR is necessary for beta(2)-AR facilitation of M71 plasma membrane localization. These studies shed light on the specificity of OR interactions with other GPCRs and the mechanisms governing olfactory receptor trafficking.
authors.affiliation: Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Cristina F
authors.initials: CF
authors.lastname: Bush
authors.forename: Seth V
authors.initials: SV
authors.lastname: Jones
authors.forename: Alicia N
authors.initials: AN
authors.lastname: Lyle
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Minneman
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
authors.forename: Randy A
authors.initials: RA
authors.lastname: Hall
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D007763:Lac Operon; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018034:Olfactory Receptor Neurons / Q000502:physiology; D017319:Photosensitizing Agents / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018035:Receptors, Odorant / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2
chemical_list: C547768:ADRA2A protein, human; D000098:Acetophenones; C547769:Adra2a protein, mouse; C547770:Adra2a protein, rat; C502656:Olfr151 protein, mouse; C546382:P2RY1 protein, human; C546385:P2RY2 protein, human; C546383:P2ry1 protein, mouse; C546384:P2ry1 protein, rat; C546386:P2ry2 protein, mouse; C546387:P2ry2 protein, rat; D017319:Photosensitizing Agents; D018341:Receptors, Adrenergic, alpha-2; D018343:Receptors, Adrenergic, beta-2; D043562:Receptors, G-Protein-Coupled; D018035:Receptors, Odorant; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; C514389:odorant receptor OR17-40, human; C509506:olfactory receptor I7, rat; C038699:acetophenone