Role of Shc scaffold proteins in regulating neuronal differentiation and survival in the mouse nervous system

• Applicant: Dr. Heike Wegmeyer
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2008 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 87017441

Proper regulation of receptor-mediated signaling pathways within the cell ensures the correct integration and redistribution of signals from the extracellular environment. Modulatory docking proteins secure the regulation of a variety of signaling molecules. How these proteins manage to organize the precise spatial and temporal distribution of their targets, and thus, to maintain the balance between various signaling cascades, remains to be understood. I am going to take a systems level approach to understand the complex functions of hub scaffold proteins in the nervous system, involving genetics, proteomics and imaging. I will use Shc adapter proteins as a prototype to study this class of molecules. Members of the Shc protein family have been shown to regulate several receptor mediated signaling pathways, including the Ras-MAP kinase and the phosphatidylinositol (PI) 3’-kinase-Akt pathway. The most extensively studied isoform Shc1/ShcA is widely expressed in mammalian tissues, but is largely excluded from the adult nervous system, whilst the Shc2/ShcB/Sli, Shc3/ShcC/Rai/N-Shc, and Shc4/ShcD/RaLP gene products are pre-dominantly expressed in postmitotic neurons. The aims of this project are to investigate the roles of Shc2, Shc3 and Shc4 in neuronal differentiation and survival, and thereby identify redundant and specific functions of the different isoforms in the nervous system.

• DFG Programme: Research Fellowships
• International Connection: Canada
• Host: Professor Dr. Anthony J. Pawson (†)