|Research in NPlast is concerned with molecular mechanisms of cellular plasticity. Of particular interest are molecular dynamics of the postsynaptic density, signaling from synapse to nucleus and how synaptic control of nuclear gene expression feeds back to plastic properties of neurons. In this context we address how neuronal calcium signals are decoded by calcium-sensor proteins.
The postsynaptic density (PSD) of excitatory synapses is characterized by an electron-dense filamentous meshwork of cytoskeletal proteins that are thought to be crucially involved in the topological organization of synaptic signaling pathways. We are interested to learn more about the dynamics of the protein composition of the PSD and the activity-dependent remodeling of PSD structures in health and disease.
Synapses communicate with the nucleus via multiple signaling pathways. Taken together, current evidence suggests that synapse-to-nucleus signaling may exist in two phases, a quick calcium based nuclear signal to initiate a nonspecific program to remodel gene expression in response to activity, and a second, slower mechanism based on the nuclear import of synaptic or cytoplasmic proteins. We are investigating mechanisms of transport of proteins from synapse to nucleus, how these proteins regulate gene expression and how this feeds-back to synaptic function.
Ca2+ signaling in neurons is characterized by highly restricted and dynamic gradients called Ca2+ waves, spikes, transients and puffs depending upon their corresponding spatial and temporal features. The multitude of Ca2+-regulated processes requires specialized downstream processing machinery, translating the Ca2+ signal into alterations of cellular processes. We are interested in questions like which features define the functional role of EF-hand calcium sensors in neurons, the conditions that make physiological relevance of a given interaction with its target plausible, the emerging synaptic role of these proteins, and mounting evidence for their role in the regulation of protein trafficking.
For further information about the work of the Group see also the webpage of the Leibniz Group 'Dendritic organelles and Synaptic Function' at the ZMNH in Hamburg with whom we work closely together
More Information: www.kreutzlab.com