INTERACTIONS OF TAU AND MICROBTUBULES

TAU 和微管的相互作用

• 批准号: 2460480
• 负责人: MIU-FUN CHAU
• 金额: $ 3.12万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2460480
• 关键词: crosslink; intermolecular interaction; tau proteins; tubulin; yeasts

The long term goal of this work is to elucidate the underlying molecular mechanisms leading to the development of neurofibrillary tangles(NFTs), a hallmark pathological feature of Alzheimer's disease.We will focus on the microtubule associated protein, tau, known to be the major molecular component of NFTs. Whereas normal tau is capable of interacting directly with microtubules and regulating their dynamics and stability, the abnormal tau found in NFTs is unable to bind microtubules concomitant with altered structural and functional properties. This project is designed to identify critical domains of tau and tubulin involved in the tau-tubulin interaction and possibly tau-tau interaction using the yeast two-hybrid system and a covalent cross- linking biochemical assay. The information obtained in these two assays will be used to perform X-ray crystallography studies of tau and tau-tubulin co-crystals (a join effort of the Feinstein and Kohlstaedt labs) by delimiting the important domains involved in the interactions. Understanding normal tau action provides an important foundation for the study of abnormal tau action in NFTs, a critical prerequisite for the development of rational therapies to address the problem of NFT formation.

这项工作的长期目标是阐明基础 分子机制导致神经原纤维的发展 缠结（NFTS），阿尔茨海默氏症的标志性病理特征 疾病。我们将专注于微管相关的蛋白质Tau， 已知是NFT的主要分子成分。而正常的tau 能够直接与微管交互并进行调节 它们的动态和稳定性，在NFT中发现的异常Tau是 无法结合伴随的微管与结构变化和 功能性能。 该项目旨在确定tau和 涉及tau微管蛋白相互作用的微管蛋白和可能的tau-tau 使用酵母双杂交系统和共价跨 - 相互作用 连接生化测定法。这两个中获得的信息 测定将用于对TAU进行X射线晶体学研究 和tau微管蛋白共晶（Feinstein和 Kohlstaedt Labs）通过划定涉及的重要领域 互动。了解普通的tau动作提供了重要的 NFT中异常tau作用研究的基础，这是一个关键 开发理性疗法的先决条件以解决 NFT形成的问题。