科學(xué)家們發(fā)現(xiàn)了一種控制糖合成的新通道,新成果發(fā)表在日前在線出版的《自然—化學(xué)生物學(xué)》期刊上,。因為這種糖在生命中的多種作用,,新成果將廣泛應(yīng)用于全球的細(xì)胞生物學(xué)研究。
這種糖名為CD15抗原或Lewis x (Le)抗原,,經(jīng)常出現(xiàn)在細(xì)胞的表面,,對免疫系統(tǒng)和細(xì)胞的分化來說都有重要作用。到目前為止,,科學(xué)家們認(rèn)為,,當(dāng)細(xì)胞表面發(fā)出需要的信號時,細(xì)胞內(nèi)的機器會從無到有地合成出這種糖,,再將之送到細(xì)胞表面,。
sialyl—CD15是一種與糖相關(guān)的結(jié)構(gòu),它出現(xiàn)在細(xì)胞表面并攜帶有一種名為唾液酸的額外分子,。Robert Sackstein和Samah Zeineb Gadhoum發(fā)現(xiàn),,sialyl-CD15能夠被直接轉(zhuǎn)化成CD15,表明sialyl-CD15應(yīng)該是CD15的“倉庫”,。
這個令人震驚的新路線途徑意味著,,科學(xué)家們需要重新思考一個新問題:CD15和唾液酸究竟如何控制細(xì)胞功能?(生物谷Bioon.com)
生物谷推薦原始出處:
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.