Heterodimerization with β2-Adrenergic Receptors Promotes Surface Expression and Functional Activity of α1D-Adrenergic Receptors
- 22 December 2004
- journal article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in The Journal of pharmacology and experimental therapeutics
- Vol. 313 (1), 16-23
- https://doi.org/10.1124/jpet.104.079541
Abstract
The 1D-adrenergic receptor (1D-AR) is a G protein-coupled receptor (GPCR) that is poorly trafficked to the cell surface and largely nonfunctional when heterologously expressed by itself in a variety of cell types. We screened a library of approximately 30 other group I GPCRs in a quantitative luminometer assay for the ability to promote 1D-AR cell surface expression. Strik- ingly, these screens revealed only two receptors capable of inducing robust increases in the amount of 1D-AR at the cell surface: 1B-AR and 2-AR. Confocal imaging confirmed that coexpression with 2-AR resulted in translocation of 1D-AR from intracellular sites to the plasma membrane. Additionally, coimmunoprecipitation studies demonstrated that 1D-AR and 2-AR specifically interact to form heterodimers when coex- pressed in HEK-293 cells. Ligand binding studies revealed an increase in total 1D-AR binding sites upon coexpression with 2-AR, but no apparent effect on the pharmacological proper- ties of the receptors. In functional studies, coexpression with 2-AR significantly enhanced the coupling of 1D-AR to nore- pinephrine-stimulated Ca2 mobilization. Heterodimerization of 2-AR with 1D-AR also conferred the ability of 1D-AR to cointernalize upon 2-AR agonist stimulation, revealing a novel mechanism by which these different adrenergic receptor sub- types may regulate each other's activity. These findings dem- onstrate that the selective association of 1D-AR with other receptors is crucial for receptor surface expression and func- tion and also shed light on a novel mechanism of cross talk between 1- and 2-ARs that is mediated through heterodimer- ization and cross-internalization.This publication has 35 references indexed in Scilit:
- Hetero-oligomerization between GABAA and GABAB Receptors Regulates GABAB Receptor TraffickingOnline Journal of Public Health Informatics, 2004
- β- and α-adrenergic cross-signaling for L-type Ca current is impaired in transgenic mice with constitutive activation of εPKCBiochemical and Biophysical Research Communications, 2004
- The Receptors for Mammalian Sweet and Umami TasteCell, 2003
- α1d Adrenoceptor signaling is required for stimulus induced locomotor activityMolecular Psychiatry, 2003
- Transgenic studies of α1-adrenergic receptor subtype functionLife Sciences, 2002
- α1B- and α1D-Adrenergic Receptors Exhibit Different Requirements for Agonist and Mitogen-Activated Protein Kinase Activation to Regulate Growth Responses in Rat 1 FibroblastsThe Journal of pharmacology and experimental therapeutics, 2002
- Endocytosis of G protein-coupled receptors: roles of G protein-coupled receptor kinases and ß-arrestin proteinsProgress in Neurobiology, 2001
- Phosphorylation and desensitization of α1d-adrenergic receptorsBiochemical Journal, 2001
- Cell-type Specific Targeting of the α2c-AdrenoceptorOnline Journal of Public Health Informatics, 2000
- Modulation of basal intracellular calcium by inverse agonists and phorbol myristate acetate in rat‐1 fibroblasts stably expressing α1d‐adrenoceptorsFEBS Letters, 1999