Overexpression of the mouse dishevelled‐1 protein inhibits GSK‐3β‐mediated phosphorylation of tau in transfected mammalian cells

Abstract
Tau is a neuronal microtubule-associated protein whose function is modulated by phosphorylation. GSK-3β is a tau kinase. GSK-3β is part of the wingless signalling pathway and stimulation by wingless is predicted to down-regulate GSK-3β activity. In Drosophila imaginal disc cells, overexpression of dishevelled, a component of the wingless pathway, mimics the wingless signal. We have therefore studied the effect that overexpression of the murine dishevelled-1 protein has on GSK-3β-mediated phosphorylation of tau in transfected CHO cells. We find that co-transfection with dishevelled-1 is inhibitory to GSK-3β-mediated tau phosphorylation. Tau is hyperphosphorylated in Alzheimer's disease and the possible relevance of these findings to Alzheimer's disease pathogenesis are discussed.

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