論文 - 詳細
| RRC ID | 84396 |
|---|---|
| 著者 | Kondo N, Mimori-Kiyosue Y, Tokuhiro K, Pezzotti G, Kinashi T. |
| タイトル | The autophagy component LC3 regulates lymphocyte adhesion via LFA1 transport in response to outside-in signaling. |
| ジャーナル | Nat Commun |
| Abstract |
The leukocyte integrin LFA1 is indispensable for immune responses, orchestrating lymphocyte trafficking and adhesion. While LFA1 activation induces LFA1 clustering at the cell contact surface via outside-in signaling, the regulatory mechanisms remain unclear. Here, we uncovered a previously hidden function of the autophagosome component LC3 beyond its role in autophagy by bridging two seemingly unrelated pathways: LFA1 transport and autophagosome transport. LFA1 clusters co-trafficked with LC3, facilitating LFA1 accumulation at the contact surface. LC3b knockout decreased lymphocyte adhesiveness. LFA1 activation did not induce autophagy, whereas it increased mTOR and AMPK activity. LFA1-dependent AMPK activation enhances LFA1 and LC3 clustering and adhesion. Inhibiting Mst1 kinase-mediated LC3 phosphorylation promoted LC3-mediated LFA1 recruitment to the contact surface through direct interaction with RAPL, uncovering an unprecedented integrin recruitment route. These findings uncover a function of LC3 and expand our understanding of lymphocyte regulation via LFA1. |
| 巻・号 | 16(1) |
| ページ | 1343 |
| 公開日 | 2025-2-4 |
| DOI | 10.1038/s41467-025-56631-1 |
| PII | 10.1038/s41467-025-56631-1 |
| PMID | 39905041 |
| PMC | PMC11794545 |
| MeSH | AMP-Activated Protein Kinases / metabolism Animals Autophagy* Cell Adhesion Humans Lymphocyte Function-Associated Antigen-1* / genetics Lymphocyte Function-Associated Antigen-1* / metabolism Lymphocytes* / cytology Lymphocytes* / metabolism Mice Microtubule-Associated Proteins* / genetics Microtubule-Associated Proteins* / metabolism Phosphorylation Protein Transport Signal Transduction TOR Serine-Threonine Kinases / metabolism |
| IF | 12.121 |
| 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 | Bluesky |
| 各媒体での言及数の合計 | 5 |
| 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 | Ba/F3(RCB4476) |