Nanometer-scale molecular organization of neurotransmitter and hormone release sites characterized by immuno electron microscopy

• Applicant: Professor Dr. Manfred W. Kilimann
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2017 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 381877226

The interior of living cells is subtly compartmentalized and structured. In this way, counterproductive interactions are avoided and productive interactions become more efficent, precise and fast. Nerve cells, because of their elaborate cell architecture and the speed and precision of their synaptic signaling, demand a particularly high degree of molecular order. Electron microscopy allows to determine cellular structures with spatial resolution down to the size of protein molecules. It therefore lends itself to the determination of supramolecular arrangements on the nanometer scale, thus bridging the gap between the molecular and the cellular dimension.What is the spatial arrangement of proteins involved in the synaptic exocytosis of neurotransmitter vesicles? I imagine that they are precisely juxtaposed, like the cogwheels of a machine, to ensure the very fast, precise and finely controlled signal transmission at synapses. Previous immuno-electron microscopic work by my laboratory has determined the "in-situ topology" of Aczonin/Piccolo and some of its interaction partners at conventional synapses of the cerebellum. These studies are now to be extended to a specialized synapse type (ribbon synapses) and to endocrine cells, with more refined techniques. The results will lead to a better understanding how the molecular and supramolecular organization of the exocytosis machinery contributes to the specific functional properties of these synapse and cell types.

• DFG Programme: Research Grants
• Co-Investigator: Benjamin Cooper, Ph.D.