| 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
|
| リソース情報 |
| ヒト・動物細胞 |
B16 melanoma(RCB1283) |
