Koistinen Niina A, Edlund Anna K, Menon Preeti K, Ivanova Elena V, Bacanu Smaranda, Iverfeldt Kerstin
Stockholm University, Department of Neurochemistry, Stockholm, Sweden.
PLoS One. 2017 Mar 21;12(3):e0173888. doi: 10.1371/journal.pone.0173888. eCollection 2017.
Fe65 is an adaptor protein involved in both processing and signaling of the Alzheimer-associated amyloid-β precursor protein, APP. Here, the subcellular localization was further investigated using TAP-tagged Fe65 constructs expressed in human neuroblastoma cells. Our results indicate that PTB2 rather than the WW domain is important for the nuclear localization of Fe65. Electrophoretic mobility shift of Fe65 caused by phosphorylation was not detected in the nuclear fraction, suggesting that phosphorylation could restrict nuclear localization of Fe65. Furthermore, both ADAM10 and γ-secretase inhibitors decreased nuclear Fe65 in a similar way indicating an important role also of α-secretase in regulating nuclear translocation.
Fe65是一种衔接蛋白，参与阿尔茨海默病相关淀粉样前体蛋白（APP）的加工和信号传导。在此，利用在人神经母细胞瘤细胞中表达的TAP标签Fe65构建体进一步研究了其亚细胞定位。我们的结果表明，对于Fe65的核定位而言，PTB2而非WW结构域很重要。在核组分中未检测到由磷酸化引起的Fe65电泳迁移率变化，这表明磷酸化可能会限制Fe65的核定位。此外，ADAM10和γ-分泌酶抑制剂均以类似方式降低了核内Fe65，这表明α-分泌酶在调节核转位中也起重要作用。
