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

跨突触信号传导通过兴奋性突触的 ProSAP/Shank 蛋白的动态影响

• 批准号: 175663041
• 负责人: Professor Dr. Andreas Grabrucker
• 金额: --
• 依托单位: Standort Berlin
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/175663041?language=en
• 关键词: Transsynaptic; signaling; influenced; trough; dynamics

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.

ProSAP/Shank 家族的蛋白质作为兴奋性突触后的主要支架分子，通过其局部动态调节，在记忆和学习基本机制的突触可塑性中发挥重要作用。ProSAP/Shank 蛋白质的突变与疾病相关。此外，人类中 ProSAP2/Shank3 的一个拷贝的丢失很大程度上导致了 22q13 缺失综合征。 PSD 上的 ProSAP/Shank 蛋白受到 Zn2+ 的严格调控，因为 ProSAP/Shank 蛋白构建了大型平台，它们提供了大量的蛋白质相互作用位点，并且还可能能够影响突触前位点，即通过与 Neuroligins 相互作用。评估特定 ProSAP/Shank 家族成员动态在兴奋性突触中的功能作用及其对跨突触信号传导的影响 将在不同条件下研究 ProSAP/Shank 蛋白周转的变化。并将评估使用 pSDTarget 载体系统的特定 ProSAP/Shank 家族成员及其蛋白质结构域的贡献，这可能会导致对 ProSAP/Shank 蛋白质动力学及其对健康和疾病中突触信号传导的贡献有更深入的了解。