A common glycan epitope involved in neural cell differentiation and lymphocyte growth

二唾液酸（diSia）参与神经突分化以及T细胞生长，并存在于神经细胞中的一些糖蛋白如CD 166上。CD 166是一种常见于哺乳动物脑和T淋巴细胞中的细胞粘附分子;然而，diSia对CD 166的作用仍不清楚。本研究项目的目的是了解diSia表位对细胞分化和生长的调节机制。1. diSia表位刺激神经突起形成的分子机制：除了CD 166外，还鉴定了一种130 kDa的钙粘蛋白，它是一种含有diSia的糖蛋白。diSia表位存在于钙粘蛋白中的O-连接聚糖上，如CD 166。证明了至少两种负责diSia生物合成的α 2，8-唾液酸转移酶的表达。此外，diSia表位在神经突形成开始时在神经突出芽位点的脂筏中积累。因此，CD 166上的diSia表位和/或脂筏上的钙粘蛋白在功能上是重要的。2.通过diSia表位的抗原非依赖性T细胞生长的分子机制：在小鼠T细胞中，检测到100 kDa和200 kDa的糖蛋白，并且证明100 kDa的糖蛋白是CD 166。我们还证明，通过与抗diSia抗体共孵育，大大增强了通过CD 3/CD 4连接的抗原非依赖性T细胞增殖。在该条件下，糖脂和CD 166上的diSia表位均增加，同时CD 166的mRNA表达增加，可能涉及α 2，8-唾液酸转移酶。此外，糖脂和CD 166上的diSia表位在脂筏中富集，表明它们协同作用以增强T细胞增殖。

Disialic acid (diSia) is involved in neurite differentiation as well as T cell growth, and present on a few glycoproteins like CD166 in neural cells. CD166 is a cell adhesion molecule commonly occurring in mammalian brain and T lymphocytes ; however, a role of the diSia on CD166 remains unelucidated. The objective of this research project was to understand a regulatory mechanism of cell differentiation and growth by the diSia epitope. For this purpose, we have done the followings :1.Molecular mechanism for stimulation of neurite formation by the diSia epitope :In addition to CD166,a 130 kDa cadherin was identified as a diSia-containing glycoprotein. The diSia epitope is present on O-linked glycan(s) in cadherin, like CD166. The expression of at least two α2,8-sialyltransferases responsible for biosynthesis of the diSia were demonstrated. Moreover, the diSia epitope was accumulated in lipid rafts in budding sites of neurites in the beginning of neurite formation. It is thus suggested that the diSia epitope on CD166 and/or cadherin on the lipid rafts is functionally important.2.Molecular mechanism for an antigen-independent T cell growth by the diSia epitope :In mouse T cells, 100 kDa and 200 kDa glycoproteins were detected, and the 100 kDa-glycoprotein was demonstrated to be CD166. We also demonstrated that an antigen-independent T cell proliferation by the CD3/CD4-ligation was greatly enhanced by co-incubation with anti-diSia antibody. Under the conditions, the diSia epitope on both glycolipids and CD166 was increased, with a concomitant increase in expression of mRNAs for CD166,possibly involved α2,8-sialyltransferases. Furthermore, the diSia epitopes on the glycolipids and CD166 are enriched in lipid rafts, suggesting that they cooperatively operate to enhance the T-cell proliferation.