BIOSYNTHESIS AND FUNCTION OF GLYCOSPHINGOLIPIDS AND OTHER GLYCOCONJUGATES

神经节苷脂Gm 1是霍乱毒素的细胞表面受体。的 Gm 1的寡糖链被Gm 1的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酸环化酶： 环化酶系统的刺激性G蛋白的ADP-核糖基化。少 已知GM 1的脂质部分在毒素中起作用 行动上我们合成了GM 1的衍生物，其中寡糖是 与不同的脂质如磷脂、胆固醇和 脂肪胺我们在大鼠胶质瘤C6细胞上测试了衍生物， 缺乏GM 1，仅结合痕量毒素， C6细胞将新糖脂掺入血浆中， 膜，如通过霍乱毒素结合的增加来测量。然而，在这方面， 由GM 1-寡糖连接到短链组成的新糖脂 脂肪族胺不被细胞吸收;至少十二烷基胺 是必需的。新糖脂还增强了霍乱毒素 细胞的反应性，如通过增加的刺激来测量， 腺苷酸环化酶新糖脂在术语上存在差异， 每单位量的毒素结合的环AMP的量 处理的细胞。衍生自长链脂肪胺的那些， 胆固醇作为毒素受体比GM 1更有效， 衍生自磷脂的活性比GM 1的活性低。当距离 低聚糖和磷脂之间的比例增加， 间隔物，作为受体的效率降低。因此， GM 1对于霍乱毒素和这些新糖脂的作用是重要的 可以用作其他系统中GM 1生物活性的探针， 神经节苷脂的促神经突和神经营养作用。

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.