Functional analysis of a novel Rapgef5 mediated nuclear transport system

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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.