Functional analysis of a novel Rapgef5 mediated nuclear transport system

新型 Rapgef5 介导的核转运系统的功能分析

• 批准号: BB/T003766/1
• 负责人: John Griffin
• 金额: $ 60.19万
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT003766%2F1
• 关键词: Functional; analysis; novel; Rapgef5; mediated

For an embryo to develop normally, or an adult to function correctly, cells need to communicate with each other. The Wnt signaling pathway is an important cellular communication system that controls how cells behave during embryonic development and in adults. Disruption of Wnt signaling causes birth defects and diseases, including cancers. The critical step in the Wnt pathway requires the movement of a protein called beta-catenin into the nucleus. However, despite intensive research, the mechanisms that control the movement of beta-catenin remain mysterious. We discovered that a gene called Rapgef5 functions in a previously unknown nuclear transport system, which is required for the nuclear localization of beta-catenin. Loss of Rapgef5 function disrupts Wnt signaling and impairs development of the heart and face. Here, I propose to investigate exactly how this Rapgef5 transport system functions, to confirm its role in Wnt signaling, and to determine how defects in Rapgef5 function affect embryonic development. Furthermore, I will also investigate whether the new Rapgef5 nuclear transport system is required by other proteins that move in and out of the nucleus. By investigating a novel nuclear transport system for beta-catenin this research will transform our understanding of the Wnt signaling pathway and open up new avenues of basic and therapeutic research.

为了使胚胎正常发育，或者成人正常发挥功能，细胞需要相互通信。 Wnt 信号通路是一个重要的细胞通讯系统，控制细胞在胚胎发育和成人过程中的行为。 Wnt 信号传导的破坏会导致出生缺陷和疾病，包括癌症。 Wnt 通路中的关键步骤需要一种名为 β-catenin 的蛋白质进入细胞核。然而，尽管进行了大量研究，控制β-连环蛋白运动的机制仍然是个谜。我们发现一种名为 Rapgef5 的基因在以前未知的核运输系统中发挥作用，该系统是 β-连环蛋白核定位所必需的。 Rapgef5 功能的丧失会扰乱 Wnt 信号传导并损害心脏和面部的发育。在这里，我建议准确研究 Rapgef5 转运系统的功能，确认其在 Wnt 信号传导中的作用，并确定 Rapgef5 功能缺陷如何影响胚胎发育。此外，我还将研究进出细胞核的其他蛋白质是否需要新的 Rapgef5 核运输系统。通过研究一种新型的 β-连环蛋白核转运系统，这项研究将改变我们对 Wnt 信号通路的理解，并开辟基础和治疗研究的新途径。