Regulation of mu opioid receptor internalization by the scaffold protein RanBPM

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 postnati 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 HEK29 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 beta arrestin2-GFP translocation stimulated by MOP but not alpha(1B) adrenergic receptor activation, indicating selectivity of action. Our findings suggest that RanBPM is novel MOP-interacting protein that negatively regulates receptor internalization without altering MC signaling through adenylyl cyclase. (C) 2009 Elsevier Ireland Ltd. All rights reserved.