Organization and function of inner arm dyneins

内臂动力蛋白的组织和功能

• 批准号: 6456883
• 负责人: DAVID G PENNOCK
• 金额: $ 13.24万
• 依托单位: MIAMI UNIVERSITY OXFORD
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6456883
• 关键词: Tetrahymena; chemical binding; cilium /flagellum motility; dynein ATPase; electron microscopy; gene mutation; gene targeting; ion exchange chromatography; microtubules; molecular cloning; phosphorylation; polymerase chain reaction; protein localization; protein structure function; southern blotting; western blottings

DESCRIPTION (provided by applicant) Cilia and flagella are complex microtubular organelles that are ubiquitous among eukaryotes, including humans, where they are found in the respiratory tract, the female reproductive tract and on sperm cells. Ciliary and flagellar dysfunction resulting from the absence of dynein arms has been reported to cause respiratory and fertility problems in humans and other mammals. Movement of cilia and flagella is driven by a complex group of molecular motors, the axonemal dyneins. The long-term objectives of this work are to understand how all the different dyneins are organized in ciliary axonemes and to understand the role(s) of each different dynein in ciliary motility. We will attempt to answer those questions by using targeted gene knockout techniques to introduce mutations into six genes encoding the 1-headed inner arm dynein heavy chains in the unicellular protozoan, Tetrahymena thermophila. The specific aims of this project are: I Complete targeted gene knockouts of six different Tetrahymena inner arm dynein heavy chain genes; II Determine which dynein heavy chain is encoded by each of the six mutated inner arm dynein heavy chain genes; III Assign each inner arm dynein to a specific location in the axoneme; IV Test the multi-dynein hypothesis by determining the effect(s) of the different KO mutations on cell motility and feeding. The results of this work should add to our understanding of dynein organization and function in cilia and flagella.

描述（由申请人提供） 纤毛和鞭毛是普遍存在的复杂的微管细胞器 在包括人类在内的真核生物中， 生殖道，女性生殖道和精子细胞。纤毛和鞭毛 由于动力蛋白臂的缺失而导致的功能障碍已经被报道， 导致人类和其他哺乳动物的呼吸和生育问题。运动 纤毛和鞭毛的运动是由一组复杂的分子发动机驱动的， 轴丝动力蛋白这项工作的长期目标是了解如何 所有不同的动力蛋白都组织在纤毛轴丝中， 每种不同的动力蛋白在纤毛运动中的作用。我们将尝试 通过使用靶向基因敲除技术， 突变成六个编码单头内臂动力蛋白重链的基因， 单细胞原生动物嗜热四膜虫具体目标是 项目是：I完成六种不同四膜虫的靶向基因敲除 内臂动力蛋白重链基因; II确定哪个动力蛋白重链是 由六个突变的内臂动力蛋白重链基因中的每一个编码; III 将每个内臂动力蛋白分配到轴丝中的特定位置; 多动力蛋白假说，通过确定不同KO 细胞运动和进食的突变。这项工作的结果应有助于 我们对纤毛和鞭毛中动力蛋白组织和功能的理解。