Shedding of N-acetylglucosaminyltransferase-V is regulated by maturity of cellular N-glycan.

Autor: Hirata, Tetsuya, Takata, Misaki, Tokoro, Yuko, Nakano, Miyako, Kizuka, Yasuhiko
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Zdroj: Communications Biology; 8/1/2022, Vol. 5 Issue 1, p1-15, 15p
Abstrakt: 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. Cleavage of the glycan-branching enzyme N-acetylglucosaminyltransferase-V (GnT-V) by signal peptide peptidase-like 3 (SPPL3) protease and extracellular secretion of active glycan GnT-V depend on GnT-V's own glycosylation state. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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