BIOSYNTHESIS AND FUNCTION OF GLYCOSPHINGOLIPIDS AND OTHER GLYCOCONJUGATES

神经节苷脂GM1是霍乱毒素的细胞表面受体。这个 GM1的寡糖链由B或结合亚基识别 而毒素的A亚单位通过以下方式激活腺苷环化酶 环化酶系统刺激性G蛋白的ADP-核糖化。较少 已知神经节苷脂部分在毒素中的作用(S) 行动。我们合成了GM1的衍生物，其中寡糖是 偶联到不同的脂类，如磷脂、胆固醇和 脂肪胺。我们在大鼠胶质瘤C6细胞上测试了这些衍生物 缺乏GM1，只结合微量的毒素，而且很差 对此作出反应。C6细胞将新糖脂结合到血浆中 通过膜上霍乱毒素结合量的增加来衡量。然而， 由短链连接的GM1-寡糖组成的新糖脂 脂肪胺不被细胞摄取；至少是十二胺 是必需的。新糖脂还能增强霍乱毒素。 对细胞的反应性，通过增加刺激来衡量 腺苷环化酶。新糖脂之间在术语上存在差异。 每结合一定量的毒素所形成的环状AMP的量 处理过的细胞。那些来源于长链脂肪胺和 作为毒素受体，胆固醇比GM1更有效，而那些 从磷脂中提取的GM1的效率低于GM1。当距离 低聚糖与磷脂之间的相互作用随添加量的增加而增加 间隔区，作为受体的效率降低。因此，其脂类成分 GM1对霍乱毒素和这些新糖脂的作用很重要 可能在其他系统中用作GM1生物活性的探针 神经节苷脂的神经再生和神经营养作用。

Ganglioside Gm1 is the cell surface receptor for cholera toxin. The oligosaccharide chain of Gm1 is recognized by the B or binding subunits of the toxin whereas the A subunit of the toxin activates adenylate cyclase by ADP-ribosylation of the stimulatory G protein of the cyclase system. Less is known about the role(s) that the lipid moiety of GM1 plays in toxin action. We synthesized derivatives of GM1 in which the oligosaccharide was coupled to different lipids such as phospholipids, cholesterol and aliphatic amines. We tested the derivatives on rat glioma C6 cells which are deficient in GM1, bind only traces of the toxin and are poorly responsive to it. C6 cells incorporated the neoglycolipids into the plasma membranes as measured by the increase in cholera toxin binding. However, neoglycolipids consisting of GM1-oligosaccharide attached to short chain aliphatic amines were not taken up by the cells; at least a dodecylamine was required. The neoglycolipids also conferred enhanced cholera toxin responsiveness on the cells as measured by increased stimulation of adenylate cyclase. There were differences among the neoglycolipids in terms of the amounts of cyclic AMP formed per amount of toxin bound to the treated cells. Those derived from long-chain aliphatic amines and cholesterol were more efficient than GM1 as toxin receptors whereas those derived from phospholipids were less efficient than GM1. When the distance between the oligosaccharide and the phospholipid was increased by adding spacers, the efficiency as receptors decreased. Thus, the lipid moiety of GM1 is important for the action of cholera toxin and these neoglycolipids may be useful as probes of GM1 bioactivity in other systems such as the neuritogenic and neuronotrophic effects of the ganglioside.