Downregulation of glycogen synthase kinase-3beta (GSK-3beta) protein expression during neuroblastoma IMR-32 cell...

Glycogen synthase kinase-3gamma (GSK-3beta) is a multifunctional protein kinase that phosphorylates a variety of substrates including the neuronal-specific microtubule-associated protein tau. Here we report that the down-regulation of the GSK-3beta protein is an early event in the course of the differentiation of human neuroblastoma IMR-32 cells. This decline in GSK-3beta is accompanied by a significant decrease in the phosphorylation state of tau protein. A noteworthy increase in tau protein expression also takes place later during the differentiation of IMR-32 cells. The augmented expression and diminished phosphorylation of tau protein in differentiated IMR-32 cells can be correlated with increments in the assembly of microtubules and in the association of tau with microtubules. These results suggest a contribution of a decrease in GSK-3beta to molecular events leading to neuroblastoma cell differentiation. Among these, tau protein dephosphorylation might favor microtubule stabilization within neurites.