論文 - 詳細
| RRC ID | 73645 |
|---|---|
| 著者 | Shiraki A, Shimizu S. |
| タイトル | The molecular associations in clathrin-coated pit regulate β-arrestin-mediated MAPK signaling downstream of μ-opioid receptor. |
| ジャーナル | 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. |
| 巻・号 | 640 |
| ページ | 64-72 |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) |