Reference - Detail
| RRC ID | 63119 |
|---|---|
| Author | 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. |
| Title | Glycometabolic Regulation of the Biogenesis of Small Extracellular Vesicles. |
| Journal | 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. |
| Volume | 33(2) |
| Pages | 108261 |
| Published | 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 |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 11 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | B16 melanoma(RCB1283) |