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© The Rockefeller University Press, 0021-9525/2000//83 $5.00
The Journal of Cell Biology, Volume 151, Number 1, , 2000 83-94

Dishevelled-1 Regulates Microtubule Stability

Olga Krylova^a,b, Marcus J. Messenger^a, and Patricia C. Salinas^a,b

^a The Randall Institute, King's College London, London, United Kingdom, WC2B 5RL
^b Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, United Kingdom, SW7 2AY
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AY. UK.44 020 7594 520744 020 7594 5208

Dishevelled has been implicated in the regulation of cell fate decisions, cell 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 colocalizes with axonal microtubules and sediments with brain microtubules. Expression of DVL-1 protects stable microtubules from depolymerization by nocodazole in both dividing cells and differentiated neuroblastoma cells. Deletion analyses reveal that the PDZ domain, but not the DEP domain, of DVL-1 is required for microtubule stabilization. The microtubule stabilizing function of DVL-1 is mimicked by lithium-mediated inhibition of glycogen synthase kinase-3β (GSK-3β) and blocked by expression of GSK-3β. These findings suggest that DVL-1, through GSK-3β, 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.

Key Words: WNT • granule cells • cerebellum • cytoskeleton • nocodazole

© 2000 The Rockefeller University Press

Abbreviations used in this paper: CNS, central nervous system; DVL, mouse Dishevelled; EGL, external granular layer; GAP-43, growth associated protein-43; GFP, green fluorescence protein; GSK-3β, glycogen synthase kinase-3β; GST, glutathione S-transferase protein; HA, hemagglutinin; IGL, internal granular cell layer; JNK, c-Jun NH₂-terminal protein kinase; MAP, microtubule-associated protein; MT, microtubule; NB2a, neuroblastoma 2a.

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