[Abstract Title]. - Society for Neuroscience

245. Tau and Alzheimer's disease
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 245.1/N7
Topic: C.01.h. Tau
Support: NIH Grant R03AG030060
Title: Fyn kinase regulation of Dab1 and tau phosphorylation
Authors: *S. MINAMI 1 , H.-S. HOE 1 , M. P. BURNS 1 , Y. MATSUOKA 2 , G. W. REBECK 1 ;
1 Dept Neurosci, 2 Dept Neurol., Georgetown Univ., Washington, DC
Abstract: Fyn, a Src family tyrosine kinase, has recently been implicated in the pathogenesis of
Alzheimer‟s disease. Fyn is known to be upregulated in the brains of AD patients and colocalizes
with hyperphosphorylated tau. We have recently shown that Fyn also affects APP
phosphorylation, trafficking, and processing in part through interaction with Dab1, a cytoplasmic
adaptor protein itself known to affect APP processing and decrease Aβ. Fyn is highly enriched in
lipid raft domains, so to determine whether the interaction between Fyn, Dab1, and APP
occurred in lipid rafts, we isolated lipid rafts from brains of wild-type and Fyn knock-out mice.
We found that Dab1 was distributed both in and out of lipid rafts in brains of both types of mice.
In wild-type mouse brains, tyrosine-phosphorylated Dab1 was found predominantly in lipid rafts.
However, tyrosine-phosphorylated Dab1 was observed equally in and out of lipid rafts isolated
from Fyn knock-out mice, implicating an important role for Fyn in the phosphorylation of Dab1
in lipid rafts. To examine the downstream effects of Fyn activation of Dab1, we treated primary
neurons with PP2, an inhibitor of Src family kinases, and found increased levels of Dab1 and
decreased phospho-Dab1, consistent with previously published studies, and decreased Gsk3β and
Cdk5, two major tau kinases. In addition, we probed Fyn knock-out brain homogenates for
phospho-tau and tau kinases and found decreased tau phosphorylation and decreased Cdk5
compared to wild-type mice. Together, these results suggest a role for Fyn in the pathological
processes related to APP processing and tau phosphorylation, and we will further examine how
these processes are regulated through cellular lipid rafts.
Disclosures: S. Minami , None; H. Hoe, None; M.P. Burns, None; Y. Matsuoka, None; G.W.
Rebeck, None.
Poster
245. Tau and Alzheimer's disease
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm