論文 - 詳細
| RRC ID | 89239 |
|---|---|
| 著者 | Tsuchiya M, Yagishita Y, Itakura E. |
| タイトル | GPLD1 is a scavenger carrier mediating lysosomal degradation of extracellular aberrant proteins. |
| ジャーナル | Life Sci Alliance |
| Abstract |
Loss of proteostasis leads to the accumulation of aberrant proteins, including aggregated proteins and amyloid fibrils, contributing to various diseases. Protein quality control systems are essential for maintaining proteostasis. Although intracellular mechanisms are well characterized, pathways responsible for the degradation of aberrant proteins outside the cell remain poorly understood. We previously identified the chaperone/carrier- and receptor-mediated extracellular protein degradation pathway, in which the extracellular chaperone clusterin binds misfolded proteins and the resulting complex is delivered to lysosomes via endocytosis. However, it remains unclear whether other factors are involved in this pathway. To identify novel regulators, plasma factors binding serum amyloid A1 were investigated. Glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1) was found to directly bind serum amyloid A1 and promote its lysosomal degradation. This activity was independent of GPLD1's cleavage activity for GPI-anchored proteins. Furthermore, GPLD1 mediates lysosomal degradation of misfolded proteins, with cell surface heparan sulfate acting as its receptor. Our data demonstrate that GPLD1 is a novel scavenger carrier with substrate specificity distinct from clusterin, responsible for degrading extracellular aberrant proteins. |
| 巻・号 | 9(8) |
| 公開日 | 2026-8-1 |
| DOI | 10.26508/lsa.202603717 |
| PII | 9/8/e202603717 |
| PMID | 42248661 |
| PMC | PMC13241479 |
| MeSH | Animals Clusterin / metabolism Endocytosis HEK293 Cells Humans Lysosomes* / metabolism Protein Binding Proteolysis Proteostasis |
| IF | 2.622 |
| 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 | Bluesky |
| 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 | 11.2 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2( RCB1648) |