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Dual RXR motifs regulate nerve growth factor–mediated intracellular retention of the delta opioid receptor
- 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.
- Subjects :
- Cytoplasm
Amino Acid Motifs
Intracellular Space
Golgi Apparatus
Biology
Arginine
PC12 Cells
δ-opioid receptor
03 medical and health sciences
symbols.namesake
Phosphatidylinositol 3-Kinases
Structure-Activity Relationship
0302 clinical medicine
Protein Domains
Receptors, Opioid, delta
Nerve Growth Factor
Animals
Amino Acid Sequence
Receptor
Molecular Biology
030304 developmental biology
Phosphoinositide-3 Kinase Inhibitors
Sequence Deletion
0303 health sciences
Vesicle coat
Cell Membrane
Cell Biology
COPI
Articles
Membrane transport
Golgi apparatus
Cell biology
Rats
Membrane Trafficking
symbols
Signal transduction
COP-Coated Vesicles
030217 neurology & neurosurgery
Intracellular
Protein Binding
Subjects
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