REGULATION OF KAINATE RECEPTOR RNA EDITING

对L-谷氨酸有反应的离子通道，包括一个非常重要的 类神经细胞受体。 这些配体门控离子通道调节 单价和二价阳离子梯度，并介导快速突触 应答 谷氨酸受体是分子生物学中 学习和记忆的基础强调了它们在正常学习和记忆中的关键作用。 中枢神经系统的生理学 谷氨酸受体也发挥作用 谷氨酸释放过量后神经元死亡的中心作用 与创伤或慢性疾病有关。 在这种情况下， 受体适当调节钙梯度的能力被认为 是细胞毒性的基础。 谷氨酸受体亚单位GluR-6， 由激动剂限定的谷氨酸通道的组分， 红藻氨酸盐 这个亚基也经历RNA加工事件， RNA编辑，它决定了离子的钙渗透性 含有GluR-6的通道。 本提案的目的是描述 GluR-6在小鼠大脑不同区域的编辑模式 并鉴定顺式活性和反式活性分子信号， 调节GluR-6转录本的编辑。 GluR-6基因来源于 小鼠基因组文库将用于确定顺式活性元件 在体内控制RNA编辑， 将使用细胞提取物研究参与GluR-6编辑的细胞。 这些 实验将产生重要的见解，以调节一个 代谢途径被认为与正常和 神经系统异常的生理状态。

Ion channels responsive to L-glutamate, comprise an extremely important class of neural cell receptors. These ligand-gated ion channels regulate both monovalent and divalent cation gradients, and mediate fast synaptic responses. The finding that glutamate receptors underlie the molecular basis of learning and memory emphasizes their critical role in the normal physiology of the central nervous system. Glutamate receptors also play a central role in neuronal death following excessive glutamate release associated with trauma or chronic illness. In this case the loss of the receptor's ability to properly regulate calcium gradients is believed to underlie the cytotoxicity. The glutamate receptor subunit, GluR-6, is a component of glutamate channels that are defined by the agonist, kainate. This subunit also undergoes and RNA processing event known as RNA editing, which determines the calcium permeability properties of ion channels containing GluR-6. The aim of this proposal is to characterize the patterns of GluR-6 editing in different regions of the mouse brain and to identify the cis-active and trans-active molecular signals which regulate the editing of GluR-6 transcripts. GluR-6 genes derived from a mouse genomic library will be used to determine the cis-active elements which control RNA editing in vivo, and the trans-active components involved in GluR-6 editing will be studied using cell extracts. These experiments will yield important insights into the regulation of a metabolic pathway believed to be intimately linked to both normal and aberrant physiological conditions of the nervous system.