BIOCHEMICAL MECHANISMS FOR LONG TERM POTENTIATION

长期增强的生化机制

• 批准号: 6718974
• 负责人: John David Sweatt
• 金额: $ 29.99万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6718974
• 关键词: NMDA receptors; cAMP response element binding protein; enzyme activity; enzyme induction /repression; enzyme mechanism; gene expression; genetic regulation; hippocampus; laboratory rat; learning; long term potentiation; memory; mitogen activated protein kinase; molecular psychobiology; neurophysiology; phosphorylation; potassium channel; protein kinase A; protein kinase C; protein localization; receptor coupling; voltage gated channel

DESCRIPTION: (Adapted from the Investigator's Abstract) Signal transduction via protein phosphorylation plays a critical role in learning and memory. In a prominent candidate mechanism for mammalian learning and memory, hippocampal long-term potentiation (LTP), a diverse set of protein kinases plays an important role. Thus, the cAMP-dependent protein kinase (PKA), calcium/phospholipid-dependent kinase (PKC), calcium/calmodulin-dependent protein kinase (CaMKII), and mitogen-activated protein kinase (MAP kinase) all are necessary for the induction of various phases of LTP. While great progress has been made in identifying the kinases involved in LTP, there are many gaps in our knowledge of how the protein kinases are regulated by NMDA receptor-dependent and independent processes during LTP. In addition, little is understood concerning the downstream targets of these kinases. To address this question, three specific aims are proposed: Specific Aim 1, to investigate the regulation of phosphorylation of the Shal-type K+ channel Kv4.2 in LTP, Specific Aim 2, to investigate the biochemical mechanisms for the activation of MAP kinase during LTP and Specific Aim 3, to investigate the role of protein kinases in regulating CREB phosphorylation during LTP. These studies will provide insight into mechanisms involved in long-lasting changes in neuronal function in the mammalian CNS and should increase our understanding of the molecular basis of neuropsychiatric disorders.

描述：（改编自研究者摘要） 通过蛋白质磷酸化的信号转导在蛋白质合成中起着关键作用。 学习和记忆。在哺乳动物学习的一个突出的候选机制中， 海马长时程增强（LTP），一组不同的蛋白质， 激酶起重要作用。因此，cAMP依赖性蛋白激酶（PKA）， 钙/磷脂依赖性激酶（PKC），钙/钙调蛋白依赖性 蛋白激酶（CaMKII）和促分裂原活化蛋白激酶（MAP激酶）， 是诱导LTP各个阶段所必需的。虽然取得了很大进展 目前对LTP相关激酶的研究还存在很多空白 在我们对蛋白激酶如何受NMDA调节的知识中 LTP过程中的受体依赖和非依赖过程。此外， 关于这些激酶的下游靶点的理解。为了解决这个 问题，提出了三个具体目标：具体目标1，调查 调节LTP中Shal型K+通道Kv4.2的磷酸化， 具体目标2，研究激活的生化机制， MAP激酶在LTP和特异性Aim 3中的作用，以研究蛋白质 激酶在调节CREB磷酸化过程中的LTP。这些研究将 提供了深入了解参与神经元的长期变化的机制， 在哺乳动物中枢神经系统的功能，并应增加我们的理解， 神经精神疾病的分子基础