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

ProSAP/Shank家族的蛋白质作为兴奋性突触后的主要支架分子发挥功能。通过其局部动态调节，它们在作为记忆和学习基本机制基础的突触可塑性中具有重要作用。ProSAP/Shank蛋白的突变与自闭症谱系障碍有关，在阿尔茨海默病中发现了失调。此外，ProSAP 2/Shank 3在人类中的一个拷贝的丢失高度有助于22 q13缺失综合征。PSD处的ProSAP/Shank蛋白的量通过Zn 2+严格调节。由于ProSAP/Shank蛋白构建了大的平台，它们提供了大量的蛋白质相互作用位点，并且也可能能够影响突触前位点，即通过与Neuroligins的相互作用。将在不同条件下研究ProSAP/Shank蛋白的周转变化，并评估使用pSDTarget载体系统的特定ProSAP/Shank家族成员及其蛋白结构域的贡献。这可能会导致更深入地了解ProSAP/Shank蛋白动力学及其对健康和疾病中跨突触信号传导的贡献。

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.