MECHANISM OF CA++-MEDIATED GENE EXPRESSION IN NEURONS

描述：血清反应因子(SRF)可能作为一种 神经元中活性依赖基因表达的调节器。SRF途径 激活基因表达以响应钙离子内流通过两种L类型 电压敏感钙通道(VSCCs)和N-甲基D-天冬氨酸(NMDA) 受体亚型。在神经元中，SRF似乎是NMDA的调节器 受体介导的基因表达。 建议用实验来阐明SRF的调节机制。 活性依赖的基因表达，以c-fos基因为模型系统。 在第一个目标中，将利用SRF突变体的结构/功能分析来 识别和表征钙反应结构域(S)对 PC12细胞中VSCCs的激活。在第二个目标中，c-fos/β-珠蛋白 嵌合基因将用于识别编码区序列决定因素 参与调节钙的反应，并表征它们的 作用机制。在第三个目标中，SRF参与了 C-fos活性的钙依赖性调节将在培养的 当NMDA受体通过突触活动或通过 神经递质谷氨酸。

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.