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.

一个胚胎要正常发育，或者一个成年人要正常运作，细胞之间需要相互沟通。Wnt信号通路是一个重要的细胞通讯系统，控制着胚胎发育和成人细胞的行为。Wnt信号的破坏会导致出生缺陷和包括癌症在内的疾病。Wnt通路的关键步骤需要一种叫做-连环蛋白的蛋白质进入细胞核。然而，尽管进行了深入的研究，控制-连环蛋白运动的机制仍然是个谜。我们发现一个叫做Rapgef5的基因在一个以前未知的核转运系统中起作用，这是β -连环蛋白的核定位所必需的。Rapgef5功能的丧失会破坏Wnt信号，损害心脏和面部的发育。在这里，我建议研究Rapgef5运输系统的确切功能，以确认其在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，我还将研究新的Rapgef5核转运系统是否为其他进出细胞核的蛋白质所必需。通过研究一种新的β -连环蛋白核转运系统，本研究将改变我们对Wnt信号通路的理解，并为基础和治疗研究开辟新的途径。