Heterodimerization of alpha 2A- and beta 1-adrenergic receptors.
beta- and alpha(2)-adrenergic receptors are known to exhibit substantial cross-talk and mutual regulation in tissues where they are expressed together. We have found that the beta(1)-adrenergic receptor (beta(1)AR) and alpha(2A)-adrenergic receptor (alpha(2A)AR) heterodimerize when coexpressed in cells. Immunoprecipitation studies with differentially tagged beta(1)AR and alpha(2A)AR expressed in HEK-293 cells revealed robust co-immunoprecipitation of the two receptors. Moreover, agonist stimulation of alpha(2A)AR was found to induce substantial internalization of coexpressed beta(1)AR, providing further evidence for a physical association between the two receptors in a cellular environment. Ligand binding assays examining displacement of [(3)H]dihydroalprenolol binding to the beta(1)AR by various ligands revealed that beta(1)AR pharmacological properties were significantly altered when the receptor was coexpressed with alpha(2A)AR. Finally, beta(1)AR/alpha(2A)AR heterodimerization was found to be markedly enhanced by a beta(1)AR point mutation (N15A) that blocks N-linked glycosylation of the beta(1)AR as well as by point mutations (N10A/N14A) that block N-linked glycosylation of the alpha(2A)AR. These data reveal an interaction between beta(1)AR and alpha(2A)AR that is regulated by glycosylation and that may play a key role in cross-talk and mutual regulation between these receptors.
Xu
Jianguo
J
Department of Pharmacology, Rollins Research Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
He
Junqi
J
Castleberry
Amanda M
AM
Balasubramanian
Srividya
S
Lau
Anthony G
AG
Hall
Randy A
RA
D002478:Cells, Cultured; D019281:Dimerization; D006031:Glycosylation; D006801:Humans; D011233:Precipitin Tests; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry* / Q000502:physiology; D018342:Receptors, Adrenergic, beta-1 / Q000737:chemistry* / Q000502:physiology
D018341:Receptors, Adrenergic, alpha-2; D018342:Receptors, Adrenergic, beta-1