Heparin induced dimerization of APP is primarily mediated by E1 and regulated by its acidic domain
Heparin induced dimerization of APP is primarily mediated by E1 and regulated by its acidic domain
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DOI：
10.1016/j.jsb.2014.05.006
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发表时间：
2014-07-01
影响因子：
3
通讯作者：
Than, Manuel E.
中科院分区：
文献类型：
--
作者：
Hoefgen, Sandra;Coburger, Ina;Than, Manuel E.
淀粉样前体蛋白（APP）及其细胞加工被认为是阿尔茨海默病（AD）病因学的中心环节。此外，许多生理功能已被描述为APP，包括在细胞-细胞-和细胞-ECM-粘附以及轴突生长中的作用。我们在这里显示APP的寡聚化/二聚化的分子决定因素，这是其细胞（错误）功能的核心。使用尺寸排阻色谱法（SEC），动态光散射和SEC耦合静态光散射，我们证明，APP的二聚化是积极诱导肝素介导的E1结构域的二聚化，这导致在E2的二聚体相互作用。我们还表明，酸性结构域（ACD）干扰E1的二聚化，并提出了一个模型，顺式和反式二聚化发生依赖于细胞定位和功能。(C)2014作者爱思唯尔公司出版
The amyloid precursor protein (APP) and its cellular processing are believed to be centrally involved in the etiology of Alzheimer's disease (AD). In addition, many physiological functions have been described for APP, including a role in cell-cell- and cell-ECM-adhesion as well as in axonal outgrowth. We show here the molecular determinants of the oligomerization/dimerization of APP, which is central for its cellular (mis)function. Using size exclusion chromatography (SEC), dynamic light scattering and SEC-coupled static light scattering we demonstrate that the dimerization of APP is energetically induced by a heparin mediated dimerization of the E1 domain, which results in a dimeric interaction of E2. We also show that the acidic domain (AcD) interferes with the dimerization of E1 and propose a model where both, cis- and trans-dimerization occur dependent on cellular localization and function. (C) 2014 The Authors. Published by Elsevier Inc.