科学家们发现了一种控制糖合成的新通道,新成果发表在日前在线出版的《自然—化学生物学》期刊上。因为这种糖在生命中的多种作用,新成果将广泛应用于全球的细胞生物学研究。
这种糖名为CD15抗原或Lewis x (Le)抗原,经常出现在细胞的表面,对免疫系统和细胞的分化来说都有重要作用。到目前为止,科学家们认为,当细胞表面发出需要的信号时,细胞内的机器会从无到有地合成出这种糖,再将之送到细胞表面。
sialyl—CD15是一种与糖相关的结构,它出现在细胞表面并携带有一种名为唾液酸的额外分子。Robert Sackstein和Samah Zeineb Gadhoum发现,sialyl-CD15能够被直接转化成CD15,表明sialyl-CD15应该是CD15的“仓库”。
这个令人震惊的新路线途径意味着,科学家们需要重新思考一个新问题:CD15和唾液酸究竟如何控制细胞功能?(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Chemical Biology,Samah Zeineb Gadhoum,Robert Sackstein
CD15 expression in human myeloid cell differentiation is regulated by sialidase activity
Samah Zeineb Gadhoum1,2 & Robert Sackstein1,2,3,4
The glycan determinant CD15 (also known as Lewis x, or Lex) is a distinguishing marker for human myeloid cells and mediates neutrophil adhesion to dendritic cells. Despite broad interest in this structure, the mechanisms underlying CD15 expression remain relatively uncharacterized. Accordingly, we investigated the molecular basis of increasing CD15 expression associated with human myeloid cell differentiation. Flow cytometric analysis of differentiating cells together with biochemical studies using inhibitors of glycan synthesis and of sialidases showed that increased CD15 expression is not due to de novo biosynthesis of CD15, but results predominantly from induction of (2-3)-sialidase activity, which yields CD15 from cell-surface sialyl-CD15 (also known as sialyl-Lewis x, sLex or CD15s). This differentiation-associated conversion of surface CD15s to CD15 occurs mainly on glycoproteins. Until now, modulation of post-translational glycan modifications has been attributed solely to dynamic variations in glycosyltransferase expression. Our results unveil a new paradigm by demonstrating a critical role for post-Golgi membrane glycosidase activity in the 'biosynthesis' of a key glycan determinant.