Prof. Dr. Rolf Heumann, Molecular Neurochemistry, Faculty of Chemistry
Neuronal connectivity is regulated not only during development but also in the adult brain, in response to brain activity. The small GTPase protein Ras is a universal intracellular signaling protein that may mediate such mechanisms of brain plasticity through transient activation of downstream protein phosphorylation signaling cascades. We have developed a synRas animal model expressing permanently activated Val12 Ras, selectively in neurons. Using this model we investigate if neuronal Ras activity is involved in the dynamics of dendritic spine formation in brain neurons, in the regulation of synapse number and their efficiency, in the regulation of neurogenesis in the hippocampus. The latter is thought to mediate working memory processes. We also investigate what is the molecular mechanism of Ras-mediated protection against lesion-induced neuronal degeneration. Formation of intracellular protein-protein interactions involving protein tyrosine phosphatases are studied in vivo and in vitro. The molecular mechanisms are analyzed by protein nuclear magnetic resonance structure determinations and mass spectrometric methods.