Transsynaptic signaling influenced trough the dynamics of ProSAP/Shank proteins at excitatory synapses

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Proteins of the ProSAP/Shank family function as major scaffolding molecules in excitatory post-synapses. Through their local dynamic regulation they have an essential role in synaptic plasticity underlying the basic mechanisms of memory and learning. Mutations of ProSAP/Shank proteins are associated with disorders of the autism spectrum and a dysregulation is found in Alzheimer´s disease. Furthermore, the loss of one copy of ProSAP2/Shank3 in human highly contributes to the 22q13 deletion syndrome. The amount of ProSAP/Shank proteins at the PSD is tightly regulated via Zn2+. Since ProSAP/Shank proteins build large platforms they provide a multitude of protein interaction sites and might also able to influence the pre-synaptic site i.e. via interaction with Neuroligins.This project aims to evaluate the functional role of specific ProSAP/Shank family members dynamics at excitatory synapses and their impact on trans-synaptic signaling. The change in turnover of ProSAP/Shank proteins will be investigated under different conditions and the contribution of the specific ProSAP/Shank family members and their protein domains using the pSDTarget vector system will be assessed. This might lead to a deeper understanding of ProSAP/Shank protein dynamics and their contribution to transsynaptic signaling in health and disease.