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Modeling Paracrine Noncanonical Wnt Signaling In Vitro
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Wnt-3a and Dvl induce neurite retraction by activating Rho-associated kinase

Shosei Kishida1, Hideki Yamamoto, Akira Kikuchi

  • 1Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan.

Molecular and Cellular Biology
|May 4, 2004
PubMed

Insights

Dishevelled (Dvl) protein activates Rho-kinase, impacting the planar cell polarity (PCP) pathway. This study shows Dvl and Wnt-3a regulate neurite formation via Rho-kinase in mammalian cells.

Area of Science:

  • Cell biology
  • Neuroscience
  • Molecular signaling

Background:

  • Dishevelled (Dvl) is crucial for Wnt signaling, mediating both canonical beta-catenin and noncanonical planar cell polarity (PCP) pathways.
  • Rho-associated kinase (Rho-kinase) plays a role in the PCP pathway, and its activation by Dvl in mammalian cells was investigated.

Purpose of the Study:

  • To elucidate the role of Rho-kinase in Dvl-mediated signaling within the PCP pathway.
  • To investigate the impact of Dvl and Wnt-3a on neurite outgrowth and formation through Rho-kinase activation.

Main Methods:

  • Expression of Dvl-1, Wnt-1, or Wnt-3a in COS and PC12 cells.
  • Utilized Rho-binding domain of Rho-kinase and specific inhibitors (Rho-kinase inhibitor, c-Jun N-terminal kinase inhibitor).
  • Assessed neurite outgrowth inhibition and reversal in PC12 and N1E-115 cells.

Main Results:

  • Dvl-1, Wnt-1, and Wnt-3a expression activated Rho-kinase in COS cells, an effect blocked by the Rho-binding domain of Rho-kinase.
  • Dvl-1 expression in PC12 and N1E-115 cells inhibited neurite outgrowth, dependent on Rho-kinase activation.
  • Purified Wnt-3a also activated Rho-kinase and inhibited NGF-dependent neurite outgrowth in PC12 cells.

Conclusions:

  • Wnt-3a and Dvl regulate neurite formation and outgrowth through the activation of Rho-kinase.
  • PC12 and N1E-115 cell lines are valuable models for studying the PCP pathway and its downstream effectors.

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