期刊
GLYCOBIOLOGY
卷 23, 期 6, 页码 677-689出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/glycob/cwt008
关键词
disialyl; glycomics; mass spectrometry; plasma cell differentiation; ST8Sia
资金
- Academia Sinica and Taiwan National Science Council (NSC) [99-2311-B-001-021-MY3, 101-2325-B-001-009-]
- National Research Program for Genomic Medicine (NRPGM) Core Facilities for Proteomics and Glycomics [NSC 99-3112-B-001-025, 98-3112-B-001-023]
The occurrence of a terminal disialyl motif on mammalian O-glycans is increasingly being identified through recent mass spectrometry (MS)-based glycomic profiling. In most cases, it is carried on simple core 1 structures in which both the galactose and N-acetyl galactosamine can be disialylated. In contrast, a disialyl motif on N-glycans is less readily revealed by MS mapping, since additional MS/MS analysis is required to determine the distribution of the various sialic acids on typically multisialylated complex type N-glycans. In our MS-based glycomic screening, we found that a mouse B lymphoma cell line, BCL1, ranks among those that have the highest amount of disialyl motif on its O-glycans, including those carried on CD45. More intriguingly, detailed chemical and MS/MS analyses unambiguously showed that the Neu5Gc alpha 2-8Neu5Gc disialyl motif is also present on the N-glycans and that it can be carried on the termini of polylactosaminoglycan chains, which can be further sulfated on the proximal GlcNAc, occurring alongside other monosialylated sulfated LacNAc termini. Upon silencing the expression of mouse alpha 2,8-sialyltransferase VI (ST8Sia VI), the overall disialyl content decreases significantly, but more so for that on the N-glycans than the O-glycans. ST8Sia VI was further shown to be the most significantly upregulated ST8Sia during plasma cell differentiation, which coincides with increasing content of the disialyl motif. Increasing terminal disialylation without leading to polysialylation may thus have important biological consequences awaiting further investigation. Likewise, the expression of mono-and disialylated sulfated LacNAc may constitute novel recognition codes modulating B-cell activation and differentiation.
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