N- and O-Glycans Modulate Galectin-1 Binding, CD45 Signaling, and T Cell Death
N- and O-Glycans Modulate Galectin-1 Binding, CD45 Signaling, and T Cell Death
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DOI：
10.1074/jbc.m109.066191
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发表时间：
2010-01-22
影响因子：
4.8
通讯作者：
Baum, Linda G.
中科院分区：
文献类型：
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作者：
Earl, Lesley A.;Bi, Shuguang;Baum, Linda G.
半乳糖凝集素-1是一种在胸腺中高度表达的β -半乳糖苷结合蛋白，可诱导特异性胸腺细胞亚群和活化的T细胞凋亡。半乳糖凝集素-1与几种糖蛋白受体上的N-和o -聚糖结合，包括CD7、CD43和CD45。本研究表明，通过携带N-和o -聚糖的CD45传递半乳糖凝集素-1信号，受CD45异构体表达、核心2 - o -聚糖形成和N-聚糖唾液化平衡的调节。o -聚糖通过CD45磷酸酶活性介导半乳糖凝集素-1 T细胞死亡。在表达CD45低分子量同工异构体的细胞中，半乳糖凝集素-1信号转导需要核心2 - o -聚糖（半乳糖凝集素-1的高亲和力配体）的表达，而在表达CD45高分子量同工异构体的细胞中，半乳糖凝集素-1信号转导不需要核心2 - o -聚糖，这表明大量的核心1 - o -聚糖（半乳糖凝集素-1的低亲和力配体）足以克服核心2 - o -聚糖的缺乏。此外，n-聚糖的α 2,6-唾液酰化对半乳糖凝集素-1信号传导的调节不仅依赖于CD45磷酸酶活性，而且可以通过在α 2,6-或α 2,3-连锁中附着唾液酸的酶的相对表达来调节。因此，N-和o -聚糖通过不同的机制调节半乳糖凝集素-1 T细胞死亡，不同的糖基化事件可以使胸腺细胞对半乳糖凝集素-1敏感或耐药。
Galectin-1, a beta-galactoside-binding protein highly expressed in the thymus, induces apoptosis of specific thymocyte subsets and activated T cells. Galectin-1 binds to N- and O-glycans on several glycoprotein receptors, including CD7, CD43, and CD45. Here we show that galectin-1 signaling through CD45, which carries both N- and O-glycans, is regulated by CD45 isoform expression, core 2 O-glycan formation and the balance of N- glycan sialylation. Regulation of galectin-1 T cell death by O-glycans is mediated through CD45 phosphatase activity. While galectin-1 signaling in cells expressing low molecular weight isoforms of CD45 requires expression of core 2 O-glycans (high affinity ligands for galectin-1), galectin-1 signaling in cells expressing a high molecular weight isoform of CD45 does not require core 2 O-glycans, suggesting that a larger amount of core 1 O-glycans (low affinity ligands for galectin-1) is sufficient to overcome lack of core 2 O-glycans. Furthermore, regulation of galectin-1 signaling by alpha 2,6-sialylation of N-glycans is not solely dependent on CD45 phosphatase activity and can be modulated by the relative expression of enzymes that attach sialic acid in an alpha 2,6- or alpha 2,3-linkage. Thus, N- and O-glycans modulate galectin-1 T cell death by distinct mechanisms, and different glycosylation events can render thymocytes susceptible or resistant to galectin-1.