Delta opioid receptors recycle to the membrane after sorting to the degradation path

Charfi, Iness; Abdallah, Khaled; Gendron, Louis; Piñeyro, Graciela

doi:10.1007/s00018-017-2732-5

Cited by 15 publications

(14 citation statements)

References 58 publications

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“…2d, e), suggesting that the agonistic effects of DADLE partially restored the impaired DOR level induced by ischemia. Although the specific mechanisms were unclear, there was evidence that internalized DOR induced by a delta opioid peptide was recycled to the cell membrane for a new signaling cycle via an intracellular sorting mechanism [26] and that DOR activation triggered intracellular prosurvival signaling pathways (such as the ERK cascade) to promote ischemic neuronal survival [10,12], which might be implicated in DADLE-modulated upregulation of DOR. Notably, there was a significant decrease in the DOR level following the addition of naltrindole (Fig.…”

Section: Discussionmentioning

confidence: 99%

Delta opioid peptide [d-Ala2, d-Leu5] enkephalin confers neuroprotection by activating delta opioid receptor-AMPK-autophagy axis against global ischemia

Lai

et al. 2020

Cell Biosci

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Background: Ischemic stroke poses a severe risk to human health worldwide, and currently, clinical therapies for the disease are limited. Delta opioid receptor (DOR)-mediated neuroprotective effects against ischemia have attracted increasing attention in recent years. Our previous studies revealed that DOR activation by [d-Ala2, d-Leu5] enkephalin (DADLE), a selective DOR agonist, can promote hippocampal neuronal survival on day 3 after ischemia. However, the specific molecular and cellular mechanisms underlying the DOR-induced improvements in ischemic neuronal survival remain unclear. Results: We first detected the cytoprotective effects of DADLE in an oxygen-glucose deprivation/reperfusion (OGD/R) model and observed increased viability of OGD/R SH-SY5Y neuronal cells. We also evaluated changes in the DOR level following ischemia/reperfusion (I/R) injury and DADLE treatment and found that DADLE increased DOR levels after ischemia in vivo and vitro. The effects of DOR activation on postischemic autophagy were then investigated, and the results of the animal experiment showed that DOR activation by DADLE enhanced autophagy after ischemia, as indicated by elevated LC3 II/I levels and reduced P62 levels. Furthermore, the DOR-mediated protective effects on ischemic CA1 neurons were abolished by the autophagy inhibitor 3-methyladenine (3-MA). Moreover, the results of the cell experiments revealed that DOR activation not only augmented autophagy after OGD/R injury but also alleviated autophagic flux dysfunction. The molecular pathway underlying DOR-mediated autophagy under ischemic conditions was subsequently studied, and the in vivo and vitro data showed that DOR activation elevated autophagy

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Section: Discussionmentioning

confidence: 99%

Delta opioid peptide [d-Ala2, d-Leu5] enkephalin confers neuroprotection by activating delta opioid receptor-AMPK-autophagy axis against global ischemia

Lai

et al. 2020

Cell Biosci

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“…Similarly, lysosomal sorting of the DOR and the D2 dopamine receptor is mediated by the adaptor protein GASP‐1, which couples these proteins to the ESCRT‐0 complex independent of receptor ubiquitination. Recent findings have demonstrated that the DOR can recycle from the limiting membrane of the late endosome . Interestingly, ALIX and the TIP47/Rab9 retrieval complex facilitate sorting of DOR to the trans ‐golgi network, where it can be re‐sorted to the plasma membrane.…”

Section: Direct Ubiquitination Of Gpcrs and Endo‐lysosomal Sortingmentioning

confidence: 99%

“…Recent findings have demonstrated that the DOR can recycle from the limiting membrane of the late endosome . Interestingly, ALIX and the TIP47/Rab9 retrieval complex facilitate sorting of DOR to the trans ‐golgi network, where it can be re‐sorted to the plasma membrane. These findings demonstrate that ALIX, GASP‐1 and potentially other late endosomal adaptor proteins can mediate the endo‐lysosomal trafficking, in some cases independent of ubiquitin and certain canonical ESCRT components, expanding the diversity of lysosomal sorting mechanisms for GPCRs beyond the direct ubiquitination and canonical ESCRTs.…”

Section: Direct Ubiquitination Of Gpcrs and Endo‐lysosomal Sortingmentioning

confidence: 99%

“…Recent findings have demonstrated that the DOR can recycle from the limiting membrane of the late endosome. 19 Interestingly, ALIX and the TIP47/Rab9 retrieval complex facilitate sorting of DOR is recruited by β-arrestin to directly ubiquitinate β2-AR, MOR and V2R. β-arrestin is ubiquitinated by MDM2 and deubiquitinated by USP33.…”

Section: Direct Ubiquitination Of Gpcrs and Endo-lysosomal Sortingmentioning

confidence: 99%

“…The α-arrestin ARRDC3 recruits the NEDD4-family E3 ligase WWP2 to ubiquitinate and activate ALIX during the lysosomal sorting of PAR1 and P2Y 1 . C-Src phosphorylates and activates NEDD4.2 which ubiquitinates PAR1 and P2Y 1 , a process required for receptor signaling to the MAPK p38 to the trans-golgi network, 19 where it can be re-sorted to the plasma membrane. These findings demonstrate that ALIX, GASP-1 and potentially other late endosomal adaptor proteins can mediate the endolysosomal trafficking, in some cases independent of ubiquitin and certain canonical ESCRT components, expanding the diversity of lysosomal sorting mechanisms for GPCRs beyond the direct ubiquitination and canonical ESCRTs.…”

Section: Direct Ubiquitination Of Gpcrs and Endo-lysosomal Sortingmentioning

confidence: 99%

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Endo‐lysosomal sorting of G‐protein‐coupled receptors by ubiquitin: Diverse pathways for G‐protein‐coupled receptor destruction and beyond

Dores

Trejo

2018

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Ubiquitin is covalently attached to substrate proteins in the form of a single ubiquitin moiety or polyubiquitin chains and has been generally linked to protein degradation, however, distinct types of ubiquitin linkages are also used to control other critical cellular processes like cell signaling. Over forty mammalian G protein‐coupled receptors (GPCRs) have been reported to be ubiquitinated, but despite the diverse and rich complexity of GPCR signaling, ubiquitin has been largely ascribed to receptor degradation. Indeed, GPCR ubiquitination targets the receptors for degradation by lysosome, which is mediated by the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery, and the proteasome. This has led to the view that ubiquitin and ESCRTs primarily function as the signal to target GPCRs for destruction. Contrary to this conventional view, studies indicate that ubiquitination of certain GPCRs and canonical ubiquitin‐binding ESCRTs are not required for receptor degradation and revealed that diverse and complex pathways exist to regulate endo‐lysosomal sorting of GPCRs. In other studies, GPCR ubiquitination has been shown to drive signaling and not receptor degradation and further revealed novel insight into the mechanisms by which GPCRs trigger the activity of the ubiquitination machinery. Here, we discuss the diverse pathways by which ubiquitin controls GPCR endo‐lysosomal sorting and beyond.

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Differential barcoding of opioid receptors trafficking

Degrandmaison

Grisé

Parent

et al. 2021

J of Neuroscience Research

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Over the past several years, studies have highlighted the δ-opioid receptor (DOPr) as a promising therapeutic target for chronic pain management. While exhibiting milder undesired effects than most currently prescribed opioids, its specific agonists elicit effective analgesic responses in numerous animal models of chronic pain, including inflammatory, neuropathic, diabetic, and cancer-related pain. However, as compared with the extensively studied μ-opioid receptor, the molecular mechanisms governing its trafficking remain elusive. Recent advances have denoted several significant particularities in the regulation of DOPr intracellular routing, setting it apart from the other members of the opioid receptor family. Although they share high homology, each opioid receptor subtype displays specific amino acid patterns potentially involved in the regulation of its trafficking. These precise motifs or "barcodes" are selectively recognized by regulatory proteins and therefore dictate several aspects of the itinerary of a receptor, including its anterograde transport, internalization, recycling, and degradation. With a specific focus on the regulation of DOPr trafficking, this review will discuss previously reported, as well as potential novel trafficking barcodes within the opioid and nociceptin/orphanin FQ opioid peptide receptors, and their impact in determining distinct interactomes and physiological responses.

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Delta opioid receptors recycle to the membrane after sorting to the degradation path

Cited by 15 publications

References 58 publications

Delta opioid peptide [d-Ala2, d-Leu5] enkephalin confers neuroprotection by activating delta opioid receptor-AMPK-autophagy axis against global ischemia

Delta opioid peptide [d-Ala2, d-Leu5] enkephalin confers neuroprotection by activating delta opioid receptor-AMPK-autophagy axis against global ischemia

Endo‐lysosomal sorting of G‐protein‐coupled receptors by ubiquitin: Diverse pathways for G‐protein‐coupled receptor destruction and beyond

Differential barcoding of opioid receptors trafficking

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