The Role of Ceramide Kinase in Neurosecretion

神经酰胺激酶在神经分泌中的作用

• 批准号: 6447879
• 负责人: Sandra M Bajjalieh
• 金额: $ 15.19万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-26 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6447879
• 关键词: alcohol phosphotransferase; ceramides; complementary DNA; fatty acid binding protein; immunocytochemistry; in situ hybridization; intracellular; laboratory mouse; lipid transport; neural plasticity; neural transmission; neurotransmitter transport; northern blottings; psychopharmacology; secretion; sphingolipids; synaptic vesicles; western blottings

DESCRIPTION: (provided by the applicant) Chronic drug use leads to changes in neuronal functioning that ultimately result in addiction and tolerance. Like other forms of neuronal plasticity, drug-induced adaptations include modifications of synaptic efficacy. An understanding of synaptic functioning at a molecular level is therefore a crucial first step towards identifying the molecular changes that produce addiction and tolerance. Research into the molecular basis of synaptic transmission has focused largely on proteins of the synapse. However, as in other cellular processes, lipids also play a crucial role. The larger goal of this project is to elucidate the role of sphingolipids in neurotransmitter secretion, a role suggested by the presence of a ceramide (N-acyl sphingosine) kinase on synaptic vesicles. cDNAs encoding a ceramide kinase of any kind have yet to be identified. This Stage I project aims to 1) isolate cDNAs encoding brain ceramide kinase and 2) to identify the tissue expression patterns and intracellular location of brain ceramide kinase. This work will lay the foundation for biochemical and genetic studies of the role of ceramide kianse, its substrate and its product in neurotransmission and how changes in its activity contribute to synaptic plasticity.

描述：（申请人提供） 慢性药物使用会导致神经元功能的变化，最终 导致成瘾和宽容。像其他形式的神经元可塑性一样 药物诱导的适应性包括突触功效的修饰。一个 因此，了解分子水平的突触功能是A 迈向识别产生分子变化的关键第一步 成瘾和宽容。研究突触的分子基础 传播主要集中在突触的蛋白质上。但是，如 其他细胞过程，脂质也起着至关重要的作用。更大的目标 该项目是为了阐明鞘脂在神经递质中的作用 分泌，神经酰胺（N-酰基鞘氨醇）的作用 激酶在突触囊泡上。编码任何类型的神经酰胺激酶的cDNA具有 尚待确定。我的项目旨在1）隔离cDNA编码 脑神经酰胺激酶和2）确定组织表达模式和 脑神经酰胺激酶的细胞内位置。这项工作将放置 神经酰胺Kianse作用的生化和遗传研究基金会， 其底物及其在神经传递中的产品以及其如何变化 活动有助于突触可塑性。