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Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth

Yoshimi Endo Greer1, Jeffrey S Rubin

  • 1Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

The Journal of Cell Biology
|March 23, 2011
PubMed

Insights

Casein kinase 1 delta (CK1δ) is crucial for Wnt-3a-dependent neurite outgrowth in Ewing sarcoma cells. Its centrosomal localization, not CK1ε, is essential for this process.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Dishevelled-2/3 (Dvl) proteins mediate Wnt-3a-induced neurite outgrowth in Ewing sarcoma family tumor cells.
  • Neurite extension is linked to Dvl phosphorylation, which is inhibited by the casein kinase 1 (CK1) δ/ε inhibitor IC261.

Purpose of the Study:

  • To investigate the specific roles of CK1δ and CK1ε in Wnt-3a-dependent neurite outgrowth.
  • To determine the subcellular localization and functional significance of CK1δ in this process.

Main Methods:

  • Utilized small interfering RNAs (siRNAs) to knockdown CK1δ and CK1ε.
  • Investigated Dvl phosphorylation and neurite outgrowth.
  • Performed deletion analysis to map the centrosomal localization signal (CLS) of CK1δ.
  • Employed EGFP fusion proteins and kinase domain chimeras for functional rescue experiments.

Main Results:

  • Knockdown of CK1δ, but not CK1ε, inhibited Wnt-3a-dependent neurite outgrowth.
  • CK1δ, but not CK1ε, was detected at the centrosome.
  • The C-terminal domain of CK1δ contains its CLS.
  • Displacement of CK1δ from the centrosome inhibited neurite outgrowth.
  • A CK1δ-CLS chimera rescued neurite outgrowth in CK1δ-knockdown cells.

Conclusions:

  • Centrosomal localization of CK1δ is essential for Wnt-3a-dependent neuritogenesis in Ewing sarcoma cells.
  • CK1δ plays a specific, spatially regulated role in neurite formation distinct from CK1ε.

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