The Role of Ceramide Kinase in Neurosecretion

描述：（申请人提供） 长期使用药物会导致神经功能的变化， 导致成瘾和耐受。与其他形式的神经元可塑性一样， 药物诱导的适应包括突触功效的改变。一个 因此，在分子水平上理解突触功能是一个 关键的第一步，确定产生 成瘾和宽容。突触的分子基础研究 传递主要集中在突触蛋白上。然而，正如在 在其他细胞过程中，脂质也起着至关重要的作用。的更大目标 本项目旨在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）的存在表明了这一作用 突触囊泡上的激酶。编码任何种类的神经酰胺激酶的cDNA具有 还有待确认第一阶段项目的目标是：1）分离编码 脑神经酰胺激酶和2）鉴定组织表达模式， 脑神经酰胺激酶的细胞内定位。这项工作将奠定 神经酰胺作用的生物化学和遗传学研究基金会， 它的底物和产物在神经传递中的作用， 活动有助于突触可塑性。

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.