Title:
Molecular mechanisms of neuronal survival and axonal regeneration in mutant mice with disrupted Raf activity
Project management at the University of Würzburg:
Participating scientists:
Abstract:
The Raf kinases fulfil an essential role in regulation of cell growth, cell proliferation and differentiation and prevention of cell death. Our work is focussed at understanding the molecular mechanisms that allow neuronal cells to survive during embryonic development. Using gene deficient mice, we could demonstrate that BRaf, but not CRaf, is required for the survival of embryonic sensory and motor neurons in culture. No significant difference was noted for the number of neurons that could be obtained from embryonic day 12 embryos, but the BRaf deficient neurons failed to survive in the presence of neurotrophic factors. Upon introduction of a BRaf cDNA into sensory neurons from BRaf deficient embryos survival in the presence of nerve growth factor was restored. Experiments with IAPs, a class of endogenous inhibitors of cell death identified a novel protein, NRAGE, capable to interact with XIAP. Moreover, NRAGE is able to overcome the anti-apoptotic effect of Bcl-2. Further experiments provide evidence for a role of the the mitogenic cascade in regulation of vesicle transport. The structure of SPIR, a novel protein capable to interact with MAPK, suggests a role for regulation of synaptic proteins.
Key words:
Neuronal survival
Axonal regeneration
Projekt period: from 07.2000 to 06.2003
Funding institution:
DFG ,Granting date: 23.06.2000
Publications: