L-type Calcium Channel Mediated Gene Expression

L型钙通道介导的基因表达

• 批准号: 6650017
• 负责人: JASON P WEICK
• 金额: $ 3.04万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-21 至 2006-04-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6650017
• 关键词: calcium channel; gene expression; laboratory mouse; laboratory rat; neural plasticity; predoctoral investigator; protein biosynthesis; transcription factor

DESCRIPTION (provided by applicant): We are primarily interested in determining the mechanisms by which L-type calcium channels, and not other calcium entry routes, influence neuronal plasticity via changes in gene expression and protein synthesis. Specifically, we believe different alpha1 subunits of L-type calcium channels are uniquely responsible for activation of the transcription factors CREB and NFATc4, both of which regulate cellular excitability. The experiments we will use to address this question are organized into three specific aims: 1) Determine the molecular components of (alpha1C that are necessary and sufficient for activation of CREB. 2) Establish whether it is the (alpha1C and/or alpha1D comprised L-type calcium channel that regulates NFATc4 activation. 3) Elucidate the mechanism by which L-type calcium channels regulate NFAT-dependent transcription. Our overall goal is to comprehend why the expression of many genes influencing cell excitability are tightly regulated by calcium entry specifically through L-type calcium channels. Thus, we will gain insight into the mechanisms surrounding a variety of cellular events, including those linked to development, learning and memory, hyperalgesia, drug addiction and aging.

描述（由申请人提供）：我们主要有兴趣确定L型钙通道（而不是其他钙进入途径）通过基因表达和蛋白质合成的变化来影响神经元可塑性的机制。具体而言，我们认为L型钙通道的不同α1亚基是唯一负责激活转录因子CREB和NFATC4的，这两者都调节细胞兴奋性。我们将用于解决此问题的实验分为三个具体目标： 1）确定（α1c的分子成分，这是必需的且足以激活CREB的分子成分。 2）确定是否是（α1C和/或α1D组成的L型钙通道来调节NFATC4激活。 3）阐明L型钙通道调节NFAT依赖性转录的机制。 我们的总体目标是理解为什么许多影响细胞兴奋性的基因的表达受到专门通过L型钙通道的钙进入的严格调节。因此，我们将深入了解各种细胞事件的机制，包括与发育，学习和记忆相关的那些机制，痛觉过敏，药物成瘾和衰老。