Proteomic analysis of the presynaptic active zone from APP/APLP mutant mice

APP/APLP 突变小鼠突触前活性区的蛋白质组学分析

• 批准号: 173199523
• 负责人: Professor Dr. Michael Karas
• 金额: --
• 依托单位: Institut für Pharmazeutische Chemie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/173199523?language=en
• 关键词: Proteomic; analysis; presynaptic; active; zone

Synaptic vesicles docked to the presynaptic plasma membrane comprise the exocytosiscompetent subpopulation of vesicles at the active zone. Employing subcellular fractionation of synaptosomes derived from mouse brain and a monoclonal antibody directed against an integral vesicle membrane protein, we could immunoisolate synaptic vesicles together with the attached presynaptic plasma membrane. All three members of the APP family are present in the immunoisolated active zone fraction. Our goal is to compare the proteome of the presynaptic active zone of APP/APLP-knockout mice to that of controls. In addition, we will investigate if there are differences in the posttranslational modifications of presynaptic proteins following induced synaptic activity between littermate controls and APP/APLP mutant mice. Differences in the protein profile will be analyzed and the functional consequences evaluated by a joint effort within the consortium.

突触囊泡停靠在突触前质膜上，构成了活动区的胞吐囊泡亚群。采用亚细胞分离的突触体来自小鼠大脑和针对一个完整的囊泡膜蛋白的单克隆抗体，我们可以免疫分离突触囊泡连同所附的突触前质膜。APP家族的所有三个成员都存在于免疫分离的活性区部分中。我们的目标是比较APP/APLP基因敲除小鼠与对照小鼠突触前活动区的蛋白质组。此外，我们将调查是否有差异，在翻译后修饰的突触前蛋白诱导突触活性同窝对照和APP/APLP突变小鼠之间。将分析蛋白质谱的差异，并通过联盟内的共同努力评估功能后果。