The β-Amyloid Precursor Protein Functions as a Cytosolic Anchoring Site That Prevents Fe65 Nuclear Translocation

摘要: In this study we addressed the question of intracellular localization Fe65, an adaptor protein interacting with beta-amyloid precursor (APP) and transcription factor CP2/LSF/LBP1. By using tagged Fe65 expression vectors, observed that a significant fraction is localized in nucleus transfected COS7 cells. Furthermore, isolation nuclei from untransfected PC12 cells allowed us to observe part endogenous present nuclear extract. The analysis mutant constructs demonstrated region required for its translocation includes WW domain, that, on other hand, small fragment 100 residues, including contains enough structural information target reporter (green fluorescent (GFP)-GFP) nucleus. To evaluate whether Fe65-APP interaction could affect trafficking, were cotransfected APP(695) or APP(751) GFP-Fe65 vectors. These experiments no longer translocated when overexpress APP, whereas targeting mutants, unable interact unaffected by coexpression thus suggesting APP anchors cytosol.