Analysis of the function of SUMO in the brain with a particular emphasis on synaptic transmission

• Applicant: Dr. Marilyn Tirard
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2005 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 19945169

Local protein synthesis, degradation and complex remodelling are essential for synapse formation and homeostasis. In this context, ubiquitin plays a fundamental role in synapse function by controlling protein localization, activity, and stability. Ubiquitin is not the only known peptidic protein modifier. SUMO, an acidic peptide that bears less than 20% amino acid identity has very similar three dimensional structure to that of ubiquitin and can also be covalently conjugated to target proteins. Protein sumoylation is involved in protein re-localization and competition with ubiquitination. Particularly little information is currently available concerning the function of SUMO in the brain. Recently, the sumoylation of the leak potassium channel K2P1 has been described, indicating a major role of SUMO on neuron excitability. Also, some reports suggest a link between SUMO and neurodegenerative disordered as well as with components of the endocytotic machinery but the corresponding molecular pathways are unknown and few extra-nuclear SUMO substrates have been isolated so far. As a consequence of this lack of information, the aim of the study proposed here is to determine the role of sumoylation in the brain with a particular emphasis on synaptic function. Using a combination of morphological (light and electron microscopy), mouse genetic (generation of SUMO-transgenic mouse lines), and biochemical approaches (mass spectrometric analyses of sumoylated proteins), I plan todetermine the localization of the sumoylation machinery in the brain,identify brain specific sumoylated proteins particularly at the synapse, andestablish a direct link between target protein sumoylation and neuronal activity.

• DFG Programme: Research Fellowships
• Host: Professor Dr. Nils Brose