Yu You, Li Yinan, Zhang Yan
State Key Laboratory of Membrane Biology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
Neurosci Bull. 2016 Apr;32(2):171-6. doi: 10.1007/s12264-016-0021-1. Epub 2016 Mar 9.
Alzheimer's disease (AD) is a neurodegenerative disorder in which amyloid β plaques are a pathological characteristic. Little is known about the physiological functions of amyloid β precursor protein (APP). Based on its structure as a type I transmembrane protein, it has been proposed that APP might be a receptor, but so far, no ligand has been reported. In the present study, 9 proteins binding to the extracellular domain of APP were identified using a yeast two-hybrid system. After confirming the interactions in the mammalian system, mutated PLP1, members of the FLRT protein family, and KCTD16 were shown to interact with APP. These proteins have been reported to be involved in Pelizaeus-Merzbacher disease (PMD) and axon guidance. Therefore, our results shed light on the mechanisms of physiological function of APP in AD, PMD, and axon guidance.
阿尔茨海默病（AD）是一种神经退行性疾病，其中淀粉样β斑块是其病理特征。关于淀粉样β前体蛋白（APP）的生理功能知之甚少。基于其作为I型跨膜蛋白的结构，有人提出APP可能是一种受体，但迄今为止，尚未报道有配体。在本研究中，使用酵母双杂交系统鉴定出9种与APP细胞外结构域结合的蛋白质。在确认了哺乳动物系统中的相互作用后，发现突变的PLP1、FLRT蛋白家族成员和KCTD16与APP相互作用。据报道，这些蛋白质与佩利措伊斯-梅茨巴赫病（PMD）和轴突导向有关。因此，我们的研究结果揭示了APP在AD、PMD和轴突导向中的生理功能机制。
