O. Krylova et al., Dishevelled-1 regulates microtubule stability: A new function mediated by glycogen synthase kinase-3 beta, J CELL BIOL, 151(1), 2000, pp. 83-93
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.