Open AccessNuclear localization of amyloid-β precursor protein-binding protein Fe65 is dependent on regulated intramembrane proteolysis
Author(s) -
Niina Koistinen,
Anna Edlund,
Preeti Me,
Elena V. Ivanova,
SilviuAlin Bacanu,
Kerstin Iverfeldt
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0173888
Subject(s) - signal transducing adaptor protein , nuclear localization sequence , amyloid precursor protein , phosphorylation , nuclear protein , subcellular localization , nuclear export signal , microbiology and biotechnology , amyloid precursor protein secretase , nuclear transport , proteolysis , chemistry , cell nucleus , biology , biochemistry , cytoplasm , alzheimer's disease , gene , transcription factor , enzyme , medicine , disease , pathology
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.