M4 MUSCARINIC RECEPTOR MRNA STABILITY

描述：毒蕈碱受体是许多疾病的关键参与者。 生理过程包括认知和记忆。 初步数据 表明编码不同毒蕈碱受体亚型的基因可以 进行差异化管理。 在克隆性PC 12细胞系中，m4受体 通过用NGF处理使mRNA稳定和上调。 更好的 对这一现象的理解可能与理解 阿尔茨海默病中m4受体的上调。 两种药理学 这些研究将采用分子生物学方法。 具体目标是：1. 为了确定信号传导途径 调节M4受体mRNA稳定性。 对m4受体mRNA的影响 通过药理学和遗传学操作的关键蛋白质的稳定性 研究NGF受体信号转导途径。 2. 表征3 '-非翻译区和侧翼核苷酸 调节m4受体mRNA稳定性变化的序列。 删除 将产生M4受体mRNA的嵌合cDNA构建体， 转染PC 12克隆细胞定位顺式作用元件 控制转录稳定性。 3. 描述反式作用因子 参与调节M4受体mRNA的稳定性。 本节将重点 检测和表征m4受体mRNA与 调节性反式作用蛋白因子。

DESCRIPTION: Muscarinic receptors are key participants in many physiological processes including cognition and memory. Preliminary data indicate that genes encoding the different muscarinic receptor subtypes can be differentially regulated. In the clonal PC12 cell line, m4 receptor mRNAs are stabilized and up-regulated by treatment with NGF. A better understanding of this phenomenon may be relevant to understanding the basis of m4 receptor upregulation in Alzheimer's disease. Both pharmacological and molecular approaches will be employed in these studies. The specific aims are: 1. To identify the signal transduction pathways modulating m4 receptor mRNA stability. The effects on m4 receptor mRNA stability by pharmacological and genetic manipulation of key proteins in the signal transduction pathway of NGF receptor will be studies. 2. To characterize the 3'-untranslated region and flanking nucleotides sequences regulating changes in m4 receptor mRNA stability. Deletion of chimeric cDNA constructs of the m4 receptor mRNA will be generated and transfected into PC12 clonal cell line to localize cis-acting elements controlling transcript stability. 3. To characterize trans-acting factors involved in modifying m4 receptor mRNA stability. This section will focus on detecting and characterizing interactions between m4 receptor mRNA and the regulatory trans-acting protein factors.