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）：我们主要感兴趣的是确定l型钙通道的机制，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影响神经元的可塑性。具体来说，我们认为l型钙通道的不同α 1亚基是激活转录因子CREB和NFATc4的唯一原因，这两种转录因子都调节细胞的兴奋性。我们将用来解决这个问题的实验分为三个具体目标：