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The Journal of Neuroscience, July 1, 1999, 19(13):5245-5254
Dynamic Regulation of Expression and Phosphorylation of Tau by
Fibroblast Growth Factor-2 In Neural Progenitor Cells from Adult Rat
Hippocampus
Yoshitaka
Tatebayashi ,
Khalid
Iqbal, and
Inge
Grundke-Iqbal
New York State Institute for Basic Research in Developmental
Disabilities, Staten Island, New York 10314
The nature of the extracellular signals that regulate the
expression and the phosphorylation of the microtubule-associated protein tau, which is aberrantly hyperphosphorylated in Alzheimer disease and other adult-onset neurodegenerative diseases, is not known.
We have found that neural progenitor cells from adult rat hippocampus
express adult isoforms of tau and that the expression and the
phosphorylation of tau are regulated by fibroblast growth factor-2
(FGF-2). Astrocytes that are differentiated from these cells by
stimulation with ciliary neurotrophic factor express phosphorylated tau
similarly when cultured in the presence of FGF-2. In fetal progenitor
cells that express only the fetal tau isoform, expression, but not the
phosphorylation, of this protein is regulated by FGF-2 in cultures of
higher passages. The FGF-2-mediated tau hyperphosphorylation is
inhibited by lithium, an inhibitor of glycogen synthase kinase-3
(GSK-3), but not by inhibitors of mitogen-activated protein kinase or
the cyclin-dependent kinases. Furthermore, both GSK-3 activity and the
phosphorylation of tau increase when the concentration of FGF-2 is
increased up to 40 ng/ml. These results demonstrate that proliferating
adult rat hippocampal progenitor cells express adult isoforms of tau
stably and that FGF-2 upregulates the expression and, by upregulating GSK-3 activity, the phosphorylation of tau.
Key words:
tau; fibroblast growth factor-2; glycogen synthase
kinase-3; neural progenitor cells; phosphorylation; adult tau isoforms; Alzheimer Disease
Copyright © 1999 Society for Neuroscience 0270-6474/99/19135245-10$05.00/0
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