Nuclear localization of amyloid-β precursor protein-binding protein Fe65 is dependent on regulated intramembrane proteolysis.
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.
Stockholm University, Department of Neurochemistry, Stockholm, Sweden.
Niina A
NA
Koistinen
Stockholm University, Department of Neurochemistry, Stockholm, Sweden.
Anna K
AK
Edlund
Stockholm University, Department of Neurochemistry, Stockholm, Sweden.
Preeti K
PK
Menon
Stockholm University, Department of Neurochemistry, Stockholm, Sweden.
Elena V
EV
Ivanova
Stockholm University, Department of Neurochemistry, Stockholm, Sweden.
Smaranda
S
Bacanu
Stockholm University, Department of Neurochemistry, Stockholm, Sweden.
Kerstin
http://orcid.org/0000-0002-0308-1964
K
Iverfeldt
D000072197:ADAM10 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
C091042:APBB1 protein, human; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D053829:Amyloid Precursor Protein Secretases; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human