PUBLICATION
ABIN-1 Negatively Regulates μ-Opioid Receptor Function.
- Authors
- Zhou, P., Jiang, J., Yan, H., Li, Y., Zhao, J., Wang, X., Su, R., Gong, Z.
- ID
- ZDB-PUB-171215-1
- Date
- 2017
- Source
- Molecular pharmacology 93(2): 36-48 (Journal)
- Registered Authors
- Keywords
- G protein-coupled receptors (GPCRs), Receptor internalization, cAMP
- MeSH Terms
-
- Phosphorylation
- CHO Cells
- Extracellular Signal-Regulated MAP Kinases/metabolism
- Larva
- Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology
- Rats
- Analgesics, Opioid/pharmacology
- Endocytosis
- Receptors, Opioid, mu/agonists
- Receptors, Opioid, mu/chemistry
- Receptors, Opioid, mu/metabolism
- Receptors, Opioid, mu/physiology*
- Humans
- Guanosine 5'-O-(3-Thiotriphosphate)/metabolism
- Sulfur Radioisotopes/metabolism
- Luminescent Proteins
- Ubiquitination
- Signal Transduction
- Animals
- Cricetulus
- DNA-Binding Proteins/metabolism
- DNA-Binding Proteins/physiology*
- Binding Sites
- Ligands
- Cell Line, Tumor
- Cyclic AMP/metabolism
- Zebrafish/growth & development
- PubMed
- 29237725 Full text @ Mol. Pharmacol.
Citation
Zhou, P., Jiang, J., Yan, H., Li, Y., Zhao, J., Wang, X., Su, R., Gong, Z. (2017) ABIN-1 Negatively Regulates μ-Opioid Receptor Function.. Molecular pharmacology. 93(2):36-48.
Abstract
The μ-opioid receptor (MOR) is a Gi/o protein-coupled receptor that mediates analgesic, euphoric, and reward effects. Using a bacterial two-hybrid screen, we reported that the carboxyl tail of the rat MOR associates with A20-binding inhibitor of nuclear factor κB (ABIN-1). This interaction was confirmed by direct protein-protein binding and coimmunoprecipitation of MOR and ABIN-1 proteins in cell lysates. Saturation binding studies showed that ABIN-1 had no effect on MOR binding. However, the interaction of ABIN-1 and MOR inhibited the activation of G proteins induced by DAMGO ([d-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin). MOR phosphorylation, ubiquitination, and internalization induced by DAMGO were decreased in Chinese hamster ovary cells that coexpressed MOR and ABIN-1. The suppression of forskolin-stimulated adenylyl cyclase by DAMGO was also inhibited by the interaction of ABIN-1 with MOR. In addition, extracellular signal-regulated kinase activation was also negatively regulated by overexpression of ABIN-1. These data suggest that ABIN-1 is a negative coregulator of MOR activation, phosphorylation, and internalization in vitro. ABIN-1 also inhibited morphine-induced hyperlocomotion in zebrafish larvae (AB strain). By utilization of an antisense morpholino oligonucleotide (MO) gene knockdown technology, the ABIN-1 MO-injected zebrafish larvae showed a significant increase (approximately 60%) in distance moved compared with control MO-injected larvae after acute morphine treatment (P < 0.01). Taken together, ABIN-1 negatively regulates MOR function in vitro and in vivo.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
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