RGD Reference Report - Receptor heterodimerization leads to a switch in signaling: beta-arrestin2-mediated ERK activation by mu-delta opioid receptor heterodimers. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Receptor heterodimerization leads to a switch in signaling: beta-arrestin2-mediated ERK activation by mu-delta opioid receptor heterodimers.

Authors: Rozenfeld, R  Devi, LA 
Citation: Rozenfeld R and Devi LA, FASEB J. 2007 Aug;21(10):2455-65. Epub 2007 Mar 23.
RGD ID: 8656005
Pubmed: PMID:17384143   (View Abstract at PubMed)
PMCID: PMC3131006   (View Article at PubMed Central)
DOI: DOI:10.1096/fj.06-7793com   (Journal Full-text)

Opiates are analgesics of choice in the treatment of chronic pain, but their long-term use leads to the development of physiological tolerance. Thus, understanding the mechanisms modulating the response of their receptor, the mu opioid receptor (muOR), is of great clinical relevance. Here we show that heterodimerization of muOR with delta opioid receptors (deltaOR) leads to a constitutive recruitment of beta-arrestin2 to the receptor complex resulting in changes in the spatio-temporal regulation of ERK1/2 signaling. The involvement of beta-arrestin2 is further supported by studies using beta-arrestin2 siRNA in cells endogenously expressing the heterodimers. The association of beta-arrestin2 with the heterodimer can be altered by treatment with a combination of muOR agonist (DAMGO) and deltaOR antagonist (Tipp(psi)), and this leads to a shift in the pattern of ERK1/2 phosphorylation to the pattern observed with muOR alone. These data indicate that, in the naive state, muOR-deltaOR heterodimers are in a conformation conducive to beta-arrestin-mediated signaling. Destabilization of this conformation by cotreatment with muOR and deltaOR ligands leads to a switch to a non-beta-arrestin-mediated signaling. Taken together, these results show for the first time that muOR-deltaOR heterodimers, by differentially recruiting beta-arrestin, modulate the spatio-temporal dynamics of opioid receptor signaling.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of ERK1 and ERK2 cascade involved_inIDA 8656005PMID:17384143UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Oprm1  (opioid receptor, mu 1)


Additional Information