論文 - 詳細
| RRC ID | 82551 |
|---|---|
| 著者 | Woo JH, Park SJ, Park SM, Joe EH, Jou I. |
| タイトル | Interleukin-6 signaling requires EHD1-mediated alteration of membrane rafts. |
| ジャーナル | FEBS J |
| Abstract |
Interleukin-6 (IL-6) is involved in many inflammatory diseases. IL-6 binds to membrane-bound IL-6 receptor α (IL-6Rα) (classic signaling) or soluble IL-6Rα (trans-signaling); this complex then associates with the signal-transducing membrane protein gp130. IL-6Rα and gp130 float on membrane (i.e., lipid) rafts; however, how membrane rafts regulate IL-6 signaling remains unclear. Here, we demonstrate that both IL-6 classic signaling and trans-signaling depend on membrane cholesterol, an essential raft component. Super-resolution fluorescence imaging using perfringolysin O D4 fragments that selectively bind to high cholesterol concentrations revealed that IL-6 and hyper-IL-6, a fusion protein of IL-6 and soluble IL-6Rα, induce the alteration of membrane rafts. IL-6 and hyper-IL-6 induced D4-positive raft (D4 raft) formation without affecting cholera toxin subunit B (CTB)-positive rafts (CTB rafts). Receptor clustering of IL-6Rα and gp130 and STAT3 phosphorylation occurred in D4 rafts. These results indicate that D4 rafts serve as platforms for the assembly of functional IL-6 receptor complexes. We found that Eps15 homology domain-containing protein 1 (EHD1) mediates the formation of functional IL-6 receptor complexes through D4 rafts. Overall, we uncover a novel regulatory mechanism of the EHD1-mediated alteration of membrane raft in IL-6 signaling. |
| 巻・号 | 289(19) |
| ページ | 5914-5932 |
| 公開日 | 2022-10-1 |
| DOI | 10.1111/febs.16458 |
| PMID | 35429212 |
| MeSH | Cholera Toxin* / metabolism Cholesterol / metabolism Cytokine Receptor gp130 / genetics Cytokine Receptor gp130 / metabolism Interleukin-6* / genetics Interleukin-6* / metabolism Membrane Microdomains / metabolism Membrane Proteins / metabolism Receptors, Interleukin-6 / genetics Receptors, Interleukin-6 / metabolism |
| IF | 4.392 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 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 | |
| 遺伝子材料 | pET28/His6-EGFP-D4 (RDB13961) |