MECHANISM OF NEURITE FORMATION

神经节苷脂被发现可以促进神经母细胞瘤细胞的神经再生 S 在体外，并在体内促进神经再生。最近一段时间 神经节苷脂的低聚糖部分也被发现可以增强 神经母细胞瘤细胞的神经发生，提示细胞的存在 表面受体。这一假说得到了VIAB观察的支持 E 神经视网膜细胞可以与神经节苷脂结合，神经节苷脂通过一种 胰酶敏感机制。这项提议提出了两个基本问题 关于这些观察：1)外源性神经节苷脂到底有多少 到达大脑中受损的区域，在那里它可能会增强 神经元化？2)神经节苷脂如何与 神经母细胞瘤还是神经元？要回答第一个问题，放射自显影 将进行实验，以确定标记的分布 损毁和未损毁大鼠大脑中的神经节苷脂。要回答这个问题 第二个问题，将进行实验以确定是否 神经节苷脂反应性神经母细胞瘤细胞具有细胞表面受体 能够识别适当神经节的低聚糖部分 - 边上。如果识别出受体，就会对它们进行分离和鉴定。 原代培养的神经元也将被检测是否存在 神经节苷脂-寡糖细胞表面受体。确定效果的步骤 这种相互作用对被定义为关联的“差异化”属性 随着神经元的成熟，将会受到监测。确定可能的机制 M 为了将结合传递到细胞内反应中， 神经节苷脂及其对应的寡糖对磷酸化的影响 细胞质膜的活性将被测定。

Gangliosides have been found to enhance neuritogenesis by neuroblastoma cel s in vitro , and to enhance nerve regeneration in vivo. Recently the oligosaccharide moieties of gangliosides have also been found to enhance neuritogenesis by neuroblastoma cells, suggesting the presence of a cell surface receptor. This hypothesis is supported by the observation that viab e neural retina cells can bind to gangliosides adsorbed to plastic via a trypsin sensitive mechanism. This proposal asks two fundamental questions concerning these observations: 1) how much exogenous ganglioside actually reaches the lesioned area within the brain where it putatively enhances neuritogenesis?; and 2) how does the ganglioside interact with the neuroblastoma or neuron? To answer the first question autoradiographic experiments will be carried out to determine the distribution of labeled ganglioside in the brains of lesioned and unlesioned rats. To answer the second question, experiments will be carried out to determine whether ganglioside responsive neuroblastoma cells have cell surface receptors capable of recognizing the oligosaccharide moiety of the appropriate gangli - side. If receptors are identified they will be isolated and characterized. Primary cultures of neurons will also be assayed for the presence of ganglioside-oligosaccharide cell surface receptors. To determine the effect of this interaction on "differentiation" properties defined as associated with neuronal maturation will be monitored. To determine a possible mechani m for transmitting the binding into an intracellular response, the effect of the ganglioside and the corresponding oligosaccharide on the phosphorylatio activity of the cell plasma membranes will be determined.