| RRC ID |
72314
|
| 著者 |
Hirata T, Takata M, Tokoro Y, Nakano M, Kizuka Y.
|
| タイトル |
Shedding of N-acetylglucosaminyltransferase-V is regulated by maturity of cellular N-glycan.
|
| ジャーナル |
Commun Biol
|
| Abstract |
The number of N-glycan branches on glycoproteins is closely related to the development and aggravation of various diseases. Dysregulated formation of the branch produced by N-acetylglucosaminyltransferase-V (GnT-V, also called as MGAT5) promotes cancer growth and malignancy. However, it is largely unknown how the activity of GnT-V in cells is regulated. Here, we discover that the activity of GnT-V in cells is selectively upregulated by changing cellular N-glycans from mature to immature forms. Our glycomic analysis further shows that loss of terminal modifications of N-glycans resulted in an increase in the amount of the GnT-V-produced branch. Mechanistically, shedding (cleavage and extracellular secretion) of GnT-V mediated by signal peptide peptidase-like 3 (SPPL3) protease is greatly inhibited by blocking maturation of cellular N-glycans, resulting in an increased level of GnT-V protein in cells. Alteration of cellular N-glycans hardly impairs expression or localization of SPPL3; instead, SPPL3-mediated shedding of GnT-V is shown to be regulated by N-glycans on GnT-V, suggesting that the level of GnT-V cleavage is regulated by its own N-glycan structures. These findings shed light on a mechanism of secretion-based regulation of GnT-V activity.
|
| 巻・号 |
5(1)
|
| ページ |
743
|
| 公開日 |
2022-8-1
|
| DOI |
10.1038/s42003-022-03697-y
|
| PII |
10.1038/s42003-022-03697-y
|
| PMID |
35915223
|
| PMC |
PMC9343384
|
| MeSH |
Cell Line, Tumor
Glycoproteins / chemistry
N-Acetylglucosaminyltransferases* / genetics
N-Acetylglucosaminyltransferases* / metabolism
Polysaccharides* / metabolism
|
| IF |
4.165
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539)
B16 |
