Analyse der molekularen Mechanismen, die die Stabilität der neuromuskulären Synapse in Drosophila regulieren

• Applicant: Professor Dr. Jan Pielage
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2005 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5446402

Throughout the nvervous system there is evidence that the refinement and modulation of neural circuitry is driven not only by synapse formation, but also by the regulated isassembly of previously functional synaptic connections. Very little is known about the molecular mechanisms that regulate and achieve synapse stability versus disassembly in the nervous system of any organism. We have recently demonstrated that presynaptic spectrin is necessary for synapse stabilization. Loss of the presynaptic spectrin skeleton leads to neuromuscular synapse disassembly, retraction and elimination. Here I propose to define the molecular network that is required to connect spectrin to both the synaptic plasma membrane and the actin cytoskeleton. In ohter systems such a erythrocytes and epithelial cells spectrin is linked to transmembrane proteins and the actin cytoskeleton via different adaptor proteins. In epithelial cells spectrin can be linked via the adaptor protein Ankyrin to the L1 cell adhesion molecule Neuroglian. It has also been demonstrated that the adaptor molecule Adducin regulates the formation and stability of the submembranous spectrin-actin network. Preliminary data demonstrates that both Adducin und Ankyrin are present at the Drosophila NMJ. I will use genetic, molecular and electrophysiological analyses to adress whether these genes are necessary for synapse stability.

• DFG Programme: Research Fellowships
• International Connection: USA