MECHANISM OF CA++-MEDIATED GENE EXPRESSION IN NEURONS

CA介导的神经元基因表达机制

• 批准号: 6188184
• 负责人: RAVINDRA P MISRA
• 金额: $ 10.81万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6188184
• 关键词: Animalia; NMDA receptors; PC12 cells; calcium channel; calcium flux; calcium ion; fusion gene; gene induction /repression; globin; glutamates; hippocampus; neurogenetics; neurons; nucleic acid sequence; protein structure function; protooncogene; regulatory gene; transcription factor; voltage gated channel

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.

描述：血清反应因子 (SRF) 可能充当 神经元中活性依赖性基因表达的调节因子。 SRF途径 通过 L 型激活基因表达以响应钙流入 电压敏感钙通道 (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 的调节因子 受体介导的基因表达。 提出实验来阐明 SRF 介导的机制 活性依赖性基因表达，使用 c-fos 基因作为模型系统。 第一个目标是，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 PC12 细胞中 VSCC 的激活。 在第二个目标中，c-fos/beta-globin 嵌合基因将用于鉴定编码区序列决定因素 参与调节钙反应并表征其 作用机制。 在第三个目标中，SRF 的参与 c-fos活性的钙依赖性调节将在培养物中进行检查 当 NMDA 受体被突触活动或 神经递质谷氨酸。