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家族蛋白是兴奋性突触后的主要支架分子。通过局部动态调节，它们在突触可塑性中起着重要作用，这是记忆和学习的基本机制。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一种失调。此外，人类缺失一个ProSAP2/Shank3拷贝是22q13缺失综合征的重要原因。PSD上ProSAP/Shank蛋白的数量通过Zn2+受到严格调控。由于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，也可能通过与神经球蛋白的相互作用影响突触前位点。本项目旨在评估特定ProSAP/Shank家族成员在兴奋性突触中的功能作用及其对突触间信号传导的影响。将研究不同条件下ProSAP/Shank蛋白周转的变化，并使用pSDTarget载体系统评估特定ProSAP/Shank家族成员及其蛋白结构域的贡献。这可能会导致对ProSAP/Shank蛋白动力学及其在健康和疾病中的跨突触信号传导的更深入理解。