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.

为了使胚胎正常发展，或者成年以正确起作用，细胞需要相互通信。 Wnt信号通路是一个重要的细胞通信系统，可控制细胞在胚胎发育和成年人中的表现。 Wnt信号的破坏会导致包括癌症在内的先天缺陷和疾病。 WNT途径的关键步骤需要一种称为β-catenin的蛋白质进入细胞核的运动。然而，尽管进行了深入的研究，但控制β-catenin运动的机制仍然神秘。我们发现，一个称为Rapgef5的基因在以前未知的核转运系统中起作用，这是β-catenin的核定位置所必需的。 RAPGEF5功能的丧失会破坏Wnt信号传导并损害心脏和面部的发展。在这里，我建议确切地研究这种RapGEF5传输系统如何功能，以确认其在Wnt信号传导中的作用，并确定Rapgef5功能中的缺陷如何影响胚胎发育。此外，我还将研究其他蛋白质是否需要进出核的其他蛋白质。通过研究β-catenin的新型核运输系统，这项研究将改变我们对Wnt信号通路的理解，并开辟基本和治疗研究的新途径。