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ABIN-1 Negatively Regulates μ-Opioid Receptor Function

Peilan Zhou1, Jiebing Jiang2, Hui Yan2

  • 1State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China ruibinsu@126.com zhoupeilan0502@sina.com.

Molecular Pharmacology
|December 15, 2017
PubMed

Insights

A20-binding inhibitor of nuclear factor kappa B (ABIN-1) negatively regulates the mu-opioid receptor (MOR) in vitro and in vivo. ABIN-1 inhibits MOR activation, phosphorylation, and internalization, impacting pain and reward pathways.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • The mu-opioid receptor (MOR) is a key G protein-coupled receptor involved in pain, reward, and euphoria.
  • Understanding MOR regulation is crucial for developing targeted therapeutics.
  • A20-binding inhibitor of nuclear factor kappa B (ABIN-1) is implicated in inflammatory signaling pathways.

Purpose of the Study:

  • To investigate the interaction between ABIN-1 and MOR.
  • To determine the functional consequences of this interaction on MOR signaling and cellular trafficking.
  • To assess the in vivo relevance of ABIN-1 in MOR regulation.

Main Methods:

  • Bacterial two-hybrid screening to identify interacting proteins.
  • Coimmunoprecipitation and direct protein-protein binding assays to confirm MOR-ABIN-1 interaction.
  • Cellular assays in Chinese hamster ovary (CHO) cells to measure G protein activation, adenylyl cyclase activity, and extracellular signal-regulated kinase (ERK) activation.
  • Zebrafish larvae model with antisense morpholino oligonucleotide (MO) gene knockdown to assess in vivo effects of ABIN-1 on morphine-induced hyperlocomotion.

Main Results:

  • ABIN-1 directly binds to the carboxyl tail of MOR.
  • ABIN-1 inhibits DAMGO-induced G protein activation, MOR phosphorylation, ubiquitination, and internalization.
  • ABIN-1 suppresses DAMGO-mediated inhibition of forskolin-stimulated adenylyl cyclase and negatively regulates ERK activation.
  • ABIN-1 knockdown in zebrafish larvae significantly enhances morphine-induced hyperlocomotion.

Conclusions:

  • ABIN-1 acts as a negative coregulator of MOR activation, phosphorylation, and internalization in vitro.
  • ABIN-1 modulates MOR function in vivo, impacting behavioral responses to morphine.
  • These findings reveal a novel regulatory mechanism for MOR signaling with potential therapeutic implications.

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