Back to Search Start Over

Dual RXR motifs regulate nerve growth factor–mediated intracellular retention of the delta opioid receptor

Authors :
Andrew Dates
Manojkumar A. Puthenveedu
Daniel J. Shiwarski
Stephanie E Crilly
Source :
Molecular Biology of the Cell
Publication Year :
2019
Publisher :
The American Society for Cell Biology, 2019.

Abstract

The delta opioid receptor (DOR), a physiologically relevant prototype for G protein–coupled receptors, is retained in intracellular compartments in neuronal cells. This retention is mediated by a nerve growth factor (NGF)-regulated checkpoint that delays the export of DOR from the trans-Golgi network. How DOR is selectively retained in the Golgi, in the midst of dynamic membrane transport and cargo export, is a fundamental unanswered question. Here we address this by investigating sequence elements on DOR that regulate DOR surface delivery, focusing on the C-terminal tail of DOR that is sufficient for NGF-mediated regulation. By systematic mutational analysis, we define conserved dual bi-arginine (RXR) motifs that are required for NGF- and phosphoinositide-regulated DOR export from intracellular compartments in neuroendocrine cells. These motifs were required to bind the coatomer protein I (COPI) complex, a vesicle coat complex that mediates primarily retrograde cargo traffic in the Golgi. Our results suggest that interactions of DOR with COPI, via atypical COPI motifs on the C-terminal tail, retain DOR in the Golgi. These interactions could provide a point of regulation of DOR export and delivery by extracellular signaling pathways.

Details

Language :
English
ISSN :
19394586 and 10591524
Volume :
30
Issue :
5
Database :
OpenAIRE
Journal :
Molecular Biology of the Cell
Accession number :
edsair.doi.dedup.....4bddb3df4bb504a93881c23b7d42c5be