論文 - 詳細
| RRC ID | 63119 |
|---|---|
| 著者 | Harada Y, Nakajima K, Suzuki T, Fukushige T, Kondo K, Seino J, Ohkawa Y, Suzuki T, Inoue H, Kanekura T, Dohmae N, Taniguchi N, Maruyama I. |
| タイトル | Glycometabolic Regulation of the Biogenesis of Small Extracellular Vesicles. |
| ジャーナル | Cell Rep |
| Abstract |
The biogenesis of small extracellular vesicles (sEVs) is regulated by multiple molecular machineries generating considerably heterogeneous vesicle populations, including exosomes and non-exosomal vesicles, with distinct cargo molecules. However, the role of carbohydrate metabolism in generating such vesicle heterogeneity remains largely elusive. Here, we discover that 2-deoxyglucose (2-DG), a well-known glycolysis inhibitor, suppresses the secretion of non-exosomal vesicles by impairing asparagine-linked glycosylation (N-glycosylation) in mouse melanoma cells. Mechanistically, 2-DG is metabolically incorporated into N-glycan precursors, causing precursor degradation and partial hypoglycosylation. N-glycosylation blockade by Stt3a silencing is sufficient to inhibit non-exosomal vesicle secretion. In contrast, N-glycosylation blockade barely influences exosomal secretion of tetraspanin proteins. Functionally, N-glycosylation at specific sites of the hepatocyte growth factor receptor, a cargo protein of non-exosomal vesicles, facilitates its sorting into vesicles. These results uncover a link between N-glycosylation and unconventional vesicle secretion and suggest that N-glycosylation facilitates sEV biogenesis through cargo protein sorting. |
| 巻・号 | 33(2) |
| ページ | 108261 |
| 公開日 | 2020-10-13 |
| DOI | 10.1016/j.celrep.2020.108261 |
| PII | S2211-1247(20)31250-X |
| PMID | 33053347 |
| MeSH | Animals Cell Line, Tumor Deoxyglucose / metabolism Dolichols / metabolism Exosomes / metabolism Extracellular Vesicles / metabolism* Extracellular Vesicles / ultrastructure Glycosylation Lipids / chemistry Melanoma, Experimental / metabolism Melanoma, Experimental / pathology Membrane Proteins / metabolism Mice Neoplasm Metastasis Proto-Oncogene Proteins c-met / metabolism |
| IF | 8.109 |
| 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 | 11 |
| 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 | B16 melanoma(RCB1283) |