Analysis of the zinc-dependent functions of the brain-specific protein APLP1

脑特异性蛋白 APLP1 的锌依赖性功能分析

• 批准号: 177379922
• 负责人: Dr. Daniela Kaden
• 金额: --
• 依托单位: Centre for Research in Neurodegenerative Diseases
• 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 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/177379922?language=en
• 关键词: Analysis; zinc; dependent; functions; brain

The amyloid precursor protein (APP) that is a critical component in Alzheimer’s disease, belongs to a large protein family, including the brain-specific protein APLP1, which physiological functions are not fully understood. The APP family proteins are described as putative cell-surface receptors and may exert functions in cell-cell and/or cell-cellular matrix interactions. This is underlined by evidences that APP and the APLPs are involved in cis oligomerization and that APLP1 also mediates cell-cell contacts by trans interactions. Recent findings suggest a novel zinc-dependent function of APLP1 by enhancing cis and trans interactions of APLP1 at physiological concentrations.The aim of this project is to unravel the in vivo functions of APLP1 in mouse models with a specific focus on the question how these functions depend on zinc. Therefore I will perform live cell imaging studies in the presence or absence of ligands as well as electrophysiological recordings with primary neurons and hippocampal slices. Additional biochemical analysis will complement the in vivo and in vitro data. Further I want to investigate the phenotypical changes of APLP1 knock-out mice in regard to neuronal abnormalities. Thus I will contribute to the understanding of the neuronal functions of APLP1, its possible involvements in synaptic signaling events and the role APLP1 has within the APP family.

淀粉样前体蛋白（APP）是阿尔茨海默病的关键成分，属于一个大的蛋白质家族，其中包括大脑特异性蛋白APLP1，其生理功能尚不完全清楚。 APP 家族蛋白被描述为假定的细胞表面受体，并且可以在细胞-细胞和/或细胞-细胞基质相互作用中发挥功能。有证据表明 APP 和 APLP 参与顺式寡聚化，并且 APLP1 还通过反式相互作用介导细胞与细胞的接触。最近的研究结果表明，通过增强 APLP1 在生理浓度下的顺式和反式相互作用，APLP1 具有一种新的锌依赖性功能。该项目的目的是揭示 APLP1 在小鼠模型中的体内功能，特别关注这些功能如何依赖于锌的问题。因此，我将在存在或不存在配体的情况下进行活细胞成像研究，以及使用原代神经元和海马切片进行电生理记录。额外的生化分析将补充体内和体外数据。此外，我想研究 APLP1 敲除小鼠在神经元异常方面的表型变化。因此，我将有助于理解 APLP1 的神经元功能、其可能参与突触信号传导事件以及 APLP1 在 APP 家族中的作用。