論文 - 詳細
| RRC ID | 76405 |
|---|---|
| 著者 | Tomihari A, Kiyota M, Matsuura A, Itakura E. |
| タイトル | Alpha 2-macroglobulin acts as a clearance factor in the lysosomal degradation of extracellular misfolded proteins. |
| ジャーナル | Sci Rep |
| Abstract |
Proteostasis regulates protein folding and degradation; its maintenance is essential for resistance to stress and aging. The loss of proteostasis is associated with many age-related diseases. Within the cell, molecular chaperones facilitate the refolding of misfolded proteins into their bioactive forms, thus preventing undesirable interactions and aggregation. Although the mechanisms of intracellular protein degradation pathways for intracellular misfolded proteins have been extensively studied, the protein degradation pathway for extracellular proteins remain poorly understood. In this study, we identified several misfolded proteins that are substrates for alpha 2-macroglobulin (α2M), an extracellular chaperone. We also established a lysosomal internalization assay for α2M, which revealed that α2M mediates the lysosomal degradation of extracellular misfolded proteins. Comparative analyses of α2M and clusterin, another extracellular chaperone, indicated that α2M preferentially targets aggregation-prone proteins. Thus, we present the degradation pathway of α2M, which interacts with aggregation-prone proteins for lysosomal degradation via selective internalization. |
| 巻・号 | 13(1) |
| ページ | 4680 |
| 公開日 | 2023-3-28 |
| DOI | 10.1038/s41598-023-31104-x |
| PII | 10.1038/s41598-023-31104-x |
| PMID | 36977730 |
| PMC | PMC10050189 |
| MeSH | Female Humans Lysosomes / metabolism Pregnancy Pregnancy-Associated alpha 2-Macroglobulins* / metabolism Protein Folding Proteolysis Proteostasis Transcription Factors / metabolism |
| IF | 3.998 |
| 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 | News |
| 各媒体での言及数の合計 | 21 |
| 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 | HuH-7(RCB1366) HCT116(RCB2979) HeLa A549 |
| 遺伝子材料 | pcDNA5 alpha 2M-RFP-GFP-His (RDB20287) pcDNA5 alpha 2M-ALFA-His (RDB20288) pcDNA5 alpha 2M-delta bait-RFP-GFP-His (RDB20289) |