論文 - 詳細
| RRC ID | 72874 |
|---|---|
| 著者 | Ito M, Maejima Y, Nishimura K, Nakae Y, Ono A, Iwaki-Egawa S. |
| タイトル | A role for N-glycosylation in active adenosine deaminase 2 production. |
| ジャーナル | Biochim Biophys Acta Gen Subj |
| Abstract |
BACKGROUND:Adenosine deaminase 2 (ADA2) regulates extracellular levels of adenosine and the optimal expression of ADA2 is essential for modulating the immune system. However, the mechanisms regulating the production of active ADA2 enzyme are not fully understood. In this study, we examined the role of N-glycosylation in the formation of functional structures and the secretory pathway of ADA2. METHODS:We investigated the roles of N-glycosylation in the activity, homodimerization, and secretion of ADA2 via site-directed mutagenesis and the application of N-glycosylation inhibitors. Subcellular localization of ADA2 along with the endoplasmic reticulum (ER) glucosidase inhibitor was observed under confocal fluorescence microscope. RESULTS:Inhibiting the initial N-glycosylation of ADA2 in the ER via site-directed mutagenesis or treatment with N-glycosylation inhibitors reduced the intracellular ADA2 activity and secretion. At this time, decreases in the ADA2 homodimers and ADA2 aggregation were observed in the cells. Treating the cells with castanospermine, an inhibitor of N-glycan editing in the ER, resulted in a reduction of the localization rate to the Golgi and markedly suppressed the ADA2 secretion. CONCLUSIONS:These data suggest that the initial N-glycosylation and N-glycan editing in the ER are essential for the production of an active ADA2 enzyme and proper trafficking to the extracellular space. GENERAL SIGNIFICANCE:With sufficient N-glycosylation in the ER, ADA2 exerts its function and is secreted extracellularly. |
| 巻・号 | 1866(12) |
| ページ | 130237 |
| 公開日 | 2022-12-1 |
| DOI | 10.1016/j.bbagen.2022.130237 |
| PII | S0304-4165(22)00155-6 |
| PMID | 36029899 |
| MeSH | Adenosine Deaminase* / metabolism Enzyme Inhibitors* / pharmacology Glycosylation Golgi Apparatus / metabolism Polysaccharides / metabolism |
| IF | 3.422 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) THP-1(RCB1189) |