Regulation of mu opioid receptor internalization by the scaffold protein RanBPM

Jeffery N. Talbot, Donald A. Skifter, Elisabetta Bianchi, Daniel T Monaghan, Myron Lee Toews, L. Charles Murrin

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Mu opioid receptors (MOP) are transducers of the pharmacological effects of many opioid drugs, including analgesia and tolerance/dependence. Previously, we observed increased MOP signaling during postnatal development that was not associated with increased MOP or G protein expression. A yeast two-hybrid screen of a human brain cDNA library using the MOP C-terminus as bait identified RanBPM as a potential MOP-interacting protein. RanBPM has been recognized as a multi-functional scaffold protein that interacts with a variety of signaling receptors/proteins. Co-immunoprecipitation studies in HEK293 cells indicated that RanBPM constitutively associates with MOP. Functionally, RanBPM had no effect on MOP-mediated inhibition of adenylyl cyclase, yet reduced agonist-induced endocytosis of MOP. Mechanistically, RanBPM interfered with β arrestin2-GFP translocation stimulated by MOP but not α1B-adrenergic receptor activation, indicating selectivity of action. Our findings suggest that RanBPM is a novel MOP-interacting protein that negatively regulates receptor internalization without altering MOP signaling through adenylyl cyclase.

Original languageEnglish (US)
Pages (from-to)154-158
Number of pages5
JournalNeuroscience Letters
Volume466
Issue number3
DOIs
StatePublished - Dec 11 2009

Fingerprint

mu Opioid Receptor
Proteins
Receptor-Interacting Protein Serine-Threonine Kinases
Adenylyl Cyclases
Ran binding protein 9
HEK293 Cells
Endocytosis
Transducers
Gene Library
GTP-Binding Proteins
Immunoprecipitation
Analgesia
Adrenergic Receptors
Opioid Analgesics
Yeasts
Pharmacology

Keywords

  • Internalization
  • Mu opioid receptor
  • RanBPM
  • Scaffold protein
  • Yeast two-hybrid screen
  • β Arrestin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Regulation of mu opioid receptor internalization by the scaffold protein RanBPM. / Talbot, Jeffery N.; Skifter, Donald A.; Bianchi, Elisabetta; Monaghan, Daniel T; Toews, Myron Lee; Murrin, L. Charles.

In: Neuroscience Letters, Vol. 466, No. 3, 11.12.2009, p. 154-158.

Research output: Contribution to journalArticle

Talbot, Jeffery N. ; Skifter, Donald A. ; Bianchi, Elisabetta ; Monaghan, Daniel T ; Toews, Myron Lee ; Murrin, L. Charles. / Regulation of mu opioid receptor internalization by the scaffold protein RanBPM. In: Neuroscience Letters. 2009 ; Vol. 466, No. 3. pp. 154-158.
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