CD15 expression in human myeloid cell differentiation is regulated by sialidase activity.
CD15 expression in human myeloid cell differentiation is regulated by sialidase activity.
复制标题
DOI：
10.1038/nchembio.116
复制
发表时间：
2008-12
影响因子：
14.8
通讯作者：
Sackstein, Robert
中科院分区：
文献类型：
--
作者：
Gadhoum, Samah Zeineb;Sackstein, Robert
聚糖决定簇刘易斯x（Lex/CD 15）是人髓样细胞的一种区别性标志物，并介导中性粒细胞与树突状细胞的粘附。尽管对这种结构有广泛的兴趣，但Lex/CD 15表达的潜在机制仍然相对未被表征。因此，我们研究了Lex/CD 15表达增加与人髓系细胞分化相关的分子基础。对分化细胞的流式细胞术分析以及使用聚糖合成和唾液酸酶抑制剂的生化研究表明，Lex/CD 15表达的增加不是由于Lex/CD 15的从头生物合成，而是主要由α（2，3）唾液酸酶活性的诱导导致，从细胞表面sLex/CD 15 s产生Lex/CD 15。这种表面sLex/CD 15 s向Lex/CD 15的分化相关转化主要发生在糖蛋白上。因此，翻译后聚糖修饰的调节仅归因于糖基转移酶表达的动态变化。我们的研究结果揭示了一个新的范例，展示了一个关键的聚糖决定簇的“生物合成”后高尔基体膜糖苷酶活性的关键作用。
The glycan determinant Lewis x (Lex/CD15) is a distinguishing marker for human myeloid cells and mediates neutrophil adhesion to dendritic cells. Despite broad interest in this structure, the mechanism(s) underlying Lex/CD15 expression remain relatively uncharacterized. Accordingly, we investigated the molecular basis of increasing Lex/CD15 expression associated with human myeloid cell differentiation. Flow cytometric analysis of differentiating cells together with biochemical studies employing inhibitors of glycan synthesis and of sialidases showed that increased Lex/CD15 expression was not due to de novo biosynthesis of Lex/CD15, but resulted predominantly from induction of α(2,3) sialidase activity, yielding Lex/CD15 from cell surface sLex/CD15s. This differentiation-associated conversion of surface sLex/CD15s to Lex/CD15 occurs predominantly on glycoproteins. Heretofore, modulation of post-translational glycan modifications has been attributed solely to dynamic variation(s) in glycosyltransferase expression. Our results unveil a new paradigm, demonstrating a critical role for post-Golgi membrane glycosidase activity in the “biosynthesis” of a key glycan determinant.
登录
查看更多内容
影响因子：
3
作者：
Azuma, Y;Taniguchi, A;Matsumoto, K
通讯作者：
Matsumoto, K
影响因子：
2.6
作者：
CYOPICK, P;CULLITON, R;BAKER, M
通讯作者：
BAKER, M
影响因子：
5.4
作者：
GOOI, HC;THORPE, SJ;FEIZI, T
通讯作者：
FEIZI, T
影响因子：
20.3
作者：
Charrad, RS;Gadhoum, Z;Smadja-Joffe, F
通讯作者：
Smadja-Joffe, F
影响因子：
5.2
作者：
Henderson, JK;Draper, JS;Andrews, PW
通讯作者：
Andrews, PW