Physiological function of APP dimers: neuronal transport, release and receptor interaction

APP转运和APP加工大多以单侧方式进行研究，不包括APP相互作用蛋白及其在APP转运中的作用。我们和其他人已经证明低密度脂蛋白受体相关蛋白（LRP 1）参与APP加工。我们已经表明，LRP 1的C-末端结构域通过与衔接蛋白FE 65结合负责APP加工的调节（DFG Funding PI 379/3-3）。因此，我们将研究新的LRP 1相互作用的合作伙伴对APP处理的作用。我们先前能够证明LRP 1和APP在分泌途径的早期形成复合物，APP和LRP 1一起从内质网运输到细胞表面，随后以LRP 1依赖的方式内化。因此，我们将分析LRP 1是否影响APP同源和异源二聚化的过程。Pietrzik集团在LRP 1和APP加工的细胞生物学和生物化学方面拥有长期的专业知识，而Kins集团在轴突蛋白运输和APP二聚化研究方面提供了出色的专业知识。由于两个小组的专业知识互补，将非常详细地研究脂蛋白受体对内源性APP功能的功能作用。

APP transport and APP processing have mostly been studied in a unilateral maimer, excluding APP-interacting proteins and their role in APP trafficking. We and others have demonstrated that the Low Density Lipoprotein Receptor Related Protein (LRP1) is involved in APP processing. We have shown that the C-terminal domain of LRP1 through binding to the adaptor protein FE65 is responsible for the modulation of APP processing (DFG Funding PI 379/3-3). Therefore, we will investigate the role of novel LRP1-interacting partners on APP processing. We were able to demonstrate previously that LRP1 and APP form a complex early in the secretory pathway in the way that APP and LRP1 traffic together from the endoplasmatic reticulum to the cell surface and subsequently are intemalized in an LRP1-dependent fashion. Therefore, we will analyze whether LRPl influences the process of APP homo- and heterodimerization. The Pietrzik group has a long-standing expertise in the cell biology and biochemistry of LRP1 and APP processing, while the Kins group provides an excellent expertise in axonal protein trafficking and APP dimerization studies. Due to the complementary expertise of both groups, the functional role of lipoprotein receptors on endogenous APP function will be studied in great detail.