Nuclear localization of amyloid-β precursor protein-binding protein Fe65 is dependent on regulated intramembrane proteolysis

Niina A Koistinen; Anna K Edlund; Preeti K Menon; Elena V Ivanova; Smaranda Bacanu; Kerstin Iverfeldt

doi:10.1371/journal.pone.0173888

Nuclear localization of amyloid-β precursor protein-binding protein Fe65 is dependent on regulated intramembrane proteolysis

PLoS One. 2017 Mar 21;12(3):e0173888. doi: 10.1371/journal.pone.0173888. eCollection 2017.

Authors

Niina A Koistinen¹, Anna K Edlund¹, Preeti K Menon¹, Elena V Ivanova¹, Smaranda Bacanu¹, Kerstin Iverfeldt¹

Affiliation

¹ Stockholm University, Department of Neurochemistry, Stockholm, Sweden.

Abstract

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.

MeSH terms

ADAM10 Protein / antagonists & inhibitors
ADAM10 Protein / metabolism
Active Transport, Cell Nucleus
Amyloid Precursor Protein Secretases / antagonists & inhibitors
Amyloid Precursor Protein Secretases / metabolism
Amyloid beta-Protein Precursor / chemistry
Amyloid beta-Protein Precursor / genetics
Amyloid beta-Protein Precursor / metabolism*
Cell Line
Electrophoretic Mobility Shift Assay
Humans
Membrane Proteins / antagonists & inhibitors
Membrane Proteins / metabolism
Mutagenesis
Nerve Tissue Proteins / chemistry
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Neurons / metabolism
Nuclear Proteins / chemistry
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Phosphorylation
Protein Interaction Domains and Motifs
Protein Processing, Post-Translational
Proteolysis
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Sequence Deletion

Substances

APBB1 protein, human
Amyloid beta-Protein Precursor
Membrane Proteins
Nerve Tissue Proteins
Nuclear Proteins
Recombinant Fusion Proteins
Amyloid Precursor Protein Secretases
ADAM10 Protein
ADAM10 protein, human

Grants and funding

This work was supported by the Swedish Research Couuncil (to K.I.; 521-2012-2367), and by the Foundation Olle Enkvist Byggmästare (to N.A.K.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.