The molecular function(s) of nephrocystin-4

nephrocystin-4 的分子功能

• 批准号: 231514479
• 负责人: Professor Dr. Gerd Walz
• 金额: --
• 依托单位: Klinik für Innere Medizin IV - Nephrologie und Allgemeinmedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/231514479?language=en
• 关键词: molecular; function; nephrocystin

Nephronophthisis (NPH), a hereditary disorder associated with cystic kidney disease and renal failure, has been termed ciliopathy based on the observation that the gene products (nephrocystins) localize to the primary cilium. However, the cellular pathways controlled by nephrocystins are largely unknown. This proposal aims to study the function(s) of nephrocystin-4. Using the developing Xenopus epidermis as a model system, the role of nephrocystin-4 will be analyzed in basal body docking, ciliogenesis, and ciliary polarization. Since nephrocystin-4 interacts with actin-modifying proteins, elucidating the role of nephrocystin-4 in rearrangements of the actin cytoskeleton represents another important part of this study. Addressing the question which cellular programs are controlled by nephrocystin-4, this proposal will examine the role of nephrocystin-4 in cell migration and cell orientation. The analysis of nephrocystin-4 functions will provide further insight into the pathogenesis of NPH, and may yield novel therapeutic targets.

肾病综合征（NPH）是一种与囊性肾病和肾衰竭相关的遗传性疾病，根据对基因产物（肾囊蛋白）定位于初级纤毛的观察，被称为纤毛病。然而，由肾胱氨酸控制的细胞途径在很大程度上是未知的。本研究旨在研究肾囊蛋白-4的功能。使用开发爪蟾表皮作为模型系统，肾囊蛋白-4的作用将被分析在基体对接，纤毛发生，纤毛极化。由于肾囊蛋白-4与肌动蛋白修饰蛋白相互作用，阐明肾囊蛋白-4在肌动蛋白细胞骨架重排中的作用是本研究的另一个重要部分。为了解决哪些细胞程序由肾囊蛋白-4控制的问题，本提案将研究肾囊蛋白-4在细胞迁移和细胞定向中的作用。对肾囊蛋白-4功能的分析将为NPH的发病机制提供进一步的认识，并可能产生新的治疗靶点。