Research in NPlast is concerned with molecular mechanisms of cellular plasticity. Of particular interest are the molecular dynamics of the postsynaptic density, signaling from synapse to nucleus and how the synaptic control of nuclear gene expression feeds back into the plastic properties of neurons. Another focus is on 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. In recent years we have characterized a number of different PSD protein components. 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 and it is generally accepted that synaptic activity regulates gene expression required for long-term structural changes in synapto-dendritic input. 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. This second wave of transcription factors or co-activators would generate more specific responses to defined patterns of neuronal stimulation, extrasynaptic activity, or neuromodulatory or trophic factors. 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. Based on this strict compartmentalization the Ca2+ ion provides a versatile basis for complex signaling in neuronal micro- and nanodomains. The multitude of Ca2+-regulated processes requires specialized downstream processing machinery, translating the Ca2+ signal into alterations of cellular processes. The broad range of different Ca2+-triggered phenomena in neurons, ranging from neurotransmission to gene expression, is reflected by the existence of a multitude of different Ca2+-binding proteins from which numerous belong to the EF-hand super-family. We are interested in questions like which features define the functional role of a EF-hand calcium sensor 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. Structural aspects and biophysical studies are also covered.
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