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P4‐151: BACE1 and BACE2 expression in primary cultures of neurons and astrocytes
Author(s) -
Bettegazzi Barbara,
Consonni Alessandra,
Rossi Federico Maria,
Codazzi Franca,
Grohovaz Fabio,
Zacchetti Daniele
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.718
Subject(s) - amyloid precursor protein , amyloid precursor protein secretase , translation (biology) , biology , open reading frame , neuroprotection , gene expression , amyloid beta , microbiology and biotechnology , transfection , neuroscience , messenger rna , gene , alzheimer's disease , biochemistry , medicine , peptide sequence , peptide , disease
the cDNA encoding I2NTF preceded by loxP sites framed NLS signal. The Cre recombinase and tau co-transfection allowed us by immunocytochemistry to link tau phosphorylation with I2NTF cellular localization. Results: The GST fused I2NTF pulled down PP2A catalytic subunit from rat brain extract, highlighting the direct interaction of I2NTF with PP2A. In I2NTF transfected Cos7 cells the PP2A activity was inhibited. Finally we observed by confocal microscopy an increase of tau phosphorylation when, on deletion of NLS, I2NTF was translocated from the nucleus to the cytoplasm. Conclusions: These studies demonstrate the key role played by I2PP2A cleavage in its translocation from the nucleus to the cell cytoplasm, the consequential PP2A inhibition and the pathological hyperphosphorylation of tau.