Reference - Detail
| RRC ID | 73645 |
|---|---|
| Author | Shiraki A, Shimizu S. |
| Title | The molecular associations in clathrin-coated pit regulate β-arrestin-mediated MAPK signaling downstream of μ-opioid receptor. |
| Journal | Biochem Biophys Res Commun |
| Abstract |
It has been thought that μ-opioid receptors (MOPs) activate the G protein-mediated analgesic pathway and β-arrestin 2-mediated side effect pathway; however, ligands that only minimally recruit β-arrestin 2 to MOPs may also cause opioid side effects. Moreover, such side effects have been induced in mutant mice lacking β-arrestin 2 or expressing phosphorylation-deficient MOPs that do not recruit β-arrestin 2. These findings raise the critical question of whether β-arrestin 2 recruitment to MOP triggers side effects. Here, we show that β-arrestin 1 and 2 are essential in the efficient activation of the Gi/o-mediated MAPK signaling at MOP. Moreover, the magnitude of β-arrestin-mediated signals is not correlated with the magnitude of phosphorylation of the carboxyl-terminal of MOP, which is used to evaluate the β-arrestin bias of a ligand. Instead, the molecular association with β2-adaptin and clathrin heavy chain in the formation of clathrin-coated pits is essential for β-arrestin to activate MAPK signaling. Our findings provide insights into G protein-coupled receptor-mediated signaling and further highlight a concept that the accumulation of molecules required for endocytosis is critical for activating intracellular signaling. |
| Volume | 640 |
| Pages | 64-72 |
| Published | 2023-1-15 |
| DOI | 10.1016/j.bbrc.2022.11.098 |
| PII | S0006-291X(22)01654-0 |
| PMID | 36502633 |
| MeSH | Animals Clathrin-Coated Vesicles* / metabolism Endocytosis Mice Mitogen-Activated Protein Kinase Kinases* / metabolism Phosphorylation Receptors, Opioid, mu* / metabolism beta-Arrestin 1* / genetics beta-Arrestin 1* / metabolism beta-Arrestin 2* / metabolism |
| IF | 2.985 |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 293(RCB1637) |