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Preparation of Segmented Microtubules to Study Motions Driven by the Disassembling Microtubule Ends
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Published on: March 16, 2014

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

O Krylova1, M J Messenger, P C Salinas

  • 1The Randall Institute, King's College London, London, United Kingdom.

The Journal of Cell Biology
|October 6, 2000
PubMed

Insights

Dishevelled protein DVL-1 stabilizes microtubules, a function dependent on its PDZ domain and mediated by GSK-3beta. This finding reveals a new role for Dishevelled in regulating cell polarity.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Molecular Biology

Background:

  • Dishevelled proteins regulate crucial cellular processes like cell fate, polarity, and neuronal function.
  • The precise mechanisms underlying Dishevelled protein action are not fully understood.

Purpose of the Study:

  • To investigate the cellular localization and function of the mouse Dishevelled protein, DVL-1.
  • To elucidate the role of DVL-1 in microtubule dynamics and its relationship with GSK-3beta.

Main Methods:

  • Immunofluorescence to determine cellular localization of endogenous DVL-1.
  • Biochemical assays to assess DVL-1 interaction with microtubules.
  • Expression of DVL-1 deletion mutants to identify functional domains.
  • Pharmacological inhibition and expression of GSK-3beta to study its interaction with DVL-1.

Main Results:

  • Endogenous DVL-1 was found to colocalize with axonal microtubules and co-sediment with brain microtubules.
  • DVL-1 expression protected stable microtubules from nocodazole-induced depolymerization.
  • The PDZ domain of DVL-1, but not the DEP domain, was essential for microtubule stabilization.
  • Lithium-induced inhibition of GSK-3beta mimicked DVL-1's microtubule stabilizing effect, while GSK-3beta expression blocked it.

Conclusions:

  • DVL-1 plays a significant role in regulating microtubule stability.
  • GSK-3beta is involved in the mechanism by which DVL-1 influences microtubule dynamics.
  • This newly identified function of DVL-1 in microtubule regulation has implications for understanding cell polarity.

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