Role of Neddylation in the Adult Central Nervous System: Mechanisms underlying its effects on neurotransmission, synaptic plasticity and behaviours

• Antragsteller: Dr. Damian Refojo
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2011 bis 2014
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 197930304

The aim of the present study is to characterize the role of neddylation in the adult CNS. The scope of the analysis includes the identification of novel brain specific protein targets as well as the evaluation of the role of neddylation in critical neuronal processes such as spines stability, neurotransmission and behavior Three combined approaches will be followed to fulfill this goal. 1. Studies in primary neuronal cultures to analyze the effect of neddylation on spine stability and synaptic function. This experimental set up will also be used to functionally characterize previously found targets. 2. In vivo studies: Neddylation will be genetically blocked in adult animals by the delivery of expression vectors via in utero electroporation or viral injections. In addition, conditional and inducible knock-out and transgenic mice for critical enzymes of the pathway will be used. 3. Identification of new brain specific protein targets. Hypothesis driven screenings will be performed with candidates derived from the phenotypes obtained in neuronal cultures and in vivo studies. Moreover, yeast-two-hybrid and mass-spectrometry based techniques will be used to accomplish an unbiased screening.

• DFG-Verfahren: Schwerpunktprogramme
• Teilprojekt zu: SPP 1365: The regulatory and functional network of ubiquitin family proteins