Dishevelled-1 regulates microtubule stability: A new function mediated by glycogen synthase kinase-3 beta

Dishevelled has been implicated in the regulation of cell fate decisions, c ell polarity, and neuronal function, However, the mechanism of Dishevelled action remains poorly understood. Here we examine the cellular localization and function of the mouse Dishevelled protein, DVL-1. Endogenous DVL-1 col ocalizes with axonal microtubules and sediments with brain microtubules, Ex pression of DVL-1 protects stable microtubules from depolymerization by noc odazole in both dividing cells and differentiated neuroblastoma cells. Dele tion analyses reveal that the PDZ domain, but not the DEP domain, of DVL-1 is required for microtubule stabilization. The microtubule stabilizing func tion of DVL-1 is mimicked by lithium-mediated inhibition of glycogen syntha se kinase-3 beta (GSK-3 beta) and blocked by expression of GSK-3 beta, Thes e findings suggest that DVL-1, through GSK-3 beta, can regulate microtubule dynamics. This new function of DVL-1 in controlling microtubule stability may have important implications for Dishevelled proteins in regulating cell polarity.