MECHANISM OF CA++-MEDIATED GENE EXPRESSION IN NEURONS

描述：血清反应因子（SRF）可能作为 神经元中活性依赖性基因表达的调节剂。 SRF途径 激活基因表达，以响应钙离子通过两种L型 电压敏感性钙通道（VSCC）和N-甲基-D-天冬氨酸（NMDA） 受体亚型 在神经元中，SRF似乎是NMDA的调节剂 受体介导的基因表达。 实验拟阐明的机制，SRF介导 活性依赖的基因表达，使用c-fos基因作为模型系统。 在第一个目标中，SRF突变体的结构/功能分析将用于 识别和表征钙响应结构域 PC 12细胞中VSCC的活化。 在第二个目标中，c-fos/β-珠蛋白 嵌合基因将用于鉴定编码区序列决定簇 参与调节钙反应，并表征其 作用机制。 在第三个目标中，战略成果框架参与 将在培养的细胞中检测c-fos活性的钙依赖性调节。 当NMDA受体被突触活动或被神经元激活时， 神经递质谷氨酸盐。

DESCRIPTION: The Serum Response Factor (SRF) is likely to function as a regulator of activity-dependent gene expression in neurons. The SRF pathway activates gene expression in response to calcium influx through both L-type voltage sensitive calcium channels (VSCCs) and N-methyl D-aspartate (NMDA) receptor subtypes. In neurons, SRF appears to be a regulator of NMDA receptor-mediated gene expression. Experiments are proposed to elucidate the mechanism by which SRF mediates activity-dependent gene expression, using the c-fos gene as a model system. In the first aim, structure/function analyses of SRF mutants will be used to identify and characterize calcium-responsive domain(s) in response to activation of VSCCs in PC12 cells. In the second aim, c-fos/beta-globin chimeric genes will be used to identify coding region sequence determinants involved in regulating the calcium response and to characterize their mechanism of action. In the third aim, the involvement of SRF in calcium-dependent regulation of c-fos activity will be examined in cultured neurons when NMDA receptors are activated by either synaptic activity or by the neurotransmitter glutamate.