Structural and functional studies of repulsive guidance molecule (RGM) and its receptor neogenin

• Applicant: Dr. Jan Gebauer
• Subject Area: Structural Biology
• Term: from 2009 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 163209725

Neuronal innervation is a crucial step in the development of higher organisms. Axonal pathfinding depends on attractive and repulsive guidance factors. Proteins of the RGM (repulsive guidance molecule) family are a recently characterised class of guidance factors that repel axons due to their interaction with neogenin, a cell surface receptor. Interestingly, neogenin also interacts with netrins, a family of guidance factors known to attract axons. To date only little is known about the structural details of the RGM-neogenin interaction. Furthermore, it is unclear, how neogenin integrates the two opposing signals mediated by RGMs and netrins. In this study we will characterise the interaction between RGM and neogenin by X-ray crystallography and biochemical methods to answer the following questions: 1) What is the three dimensional structure of RGMa? 2) How does RGMa bind to and activate neogenin? 3) How does netrin influence RGMa-neogenin binding? 4) Does neogenin need to be activated prior to RGMa binding?

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Erhard Hohenester