ArticleMolecular biology of the cell2019
Dual RXR motifs regulate nerve growth factor-mediated intracellular retention of the delta opioid receptor.
Article in Molecular biology of the cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 37 citations in OpenAlex.
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- Diversity and specificity in location-based signaling outputs of neuronal GPCRs.Current opinion in neurobiology · 2022Review
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- Human C1orf27 protein interacts with αThe Journal of biological chemistry · 2022Article
- Functional expression of opioid receptors and other human GPCRs in yeast engineered to produce human sterols.Nature communications · 2022Article
- Specific motifs mediate post-synaptic and surface transport of G protein-coupled receptors.iScience · 2022Article
- Mechanisms of selective G protein-coupled receptor localization and trafficking.Current opinion in cell biology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.