Visit our Expo - Redox and Inflammation signaling 2012

Session XII : Cell death and neurodegenerative diseases Poster XII, 24
Amyloid precursor protein modulates ERK1,2 signaling in glial cells.
Valentina Venezia1, Mario Nizzari1, Emanuela Repetto1, Elisabetta Violani1,
Alessandro Corsaro1, Stefano Thellung1, Valentina Villa1, Pia Carlo1, Gennaro
Schettini1, Tullio Florio1 and Claudio Russo2.
1Section of Pharmacology, Dept. Oncology, Biology and Genetics, University of Genova,
Italy. 2Dept. Health Sciences, University of Molise, Campobasso, Italy. e-mail:
venezia@unige.it
The amyloid precursor protein (APP) is a transmembrane protein with a short cytoplasmic
tail. Its location and structural features are characteristics of a receptor for extracellular
ligand. Yet, the physiological function of APP is unclear, although it is well documented that
APP’s proteolytic processing, could influence the development of Alzheimer’s disease (AD),
through the formation of membrane-bound C-terminal fragments (CTFs) and of beta-amyloid
peptides (Ab). We have recently shown that tyrosine-phosphorylated APP and CTFs may
interact with Grb2 and ShcA adaptor proteins and that this coupling occurs at a higher extent
in AD subjects only.
To study the interaction between APP or CTFs and ShcA/Grb2 and to investigate their
molecular target we have used as experimental model two different glial cell lines: H4 human
neuroglioma cells and APP/APLP null mouse embryonal fibroblast cells (MEF). Here we
show that in H4 cells APP interacts with Grb2; conversely in APP/APLP null MEF cells this
interaction is possible only after the reintroduction of human APP by transfection. We have
also shown that in MEF cells the transfection of a plasmid encoding for human APP wt
enhances the phosphorylation of ERK 1,2 as revealed by western blotting and
immunofluorescence experiments. Finally, also in H4 cells the overexpression of APP
upregulates the levels of phospho-ERK1,2.
In summary our data suggest that APP may influence phospho-ERK 1,2 signaling through its
binding with Grb2 and ShcA adaptors. The meaning of this event is not clear, but APP
interaction with these adaptors could be relevant to regulate either the physiological function
of APP or to sustain glial proliferation in Alzheimer Disease pathology.
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