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Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts

Sophie Dupre-Crochet1, Angélica Figueroa, Catherine Hogan

  • 1MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, and Department of Biology, University College London, Gower Street, London, United Kingdom.

Molecular and Cellular Biology
|March 14, 2007
PubMed

Insights

Casein kinase 1 (CK1) negatively regulates cell-cell contacts by phosphorylating E-cadherin. CK1 inhibition stabilizes these adhesions, while CK1 overexpression disrupts them, revealing a novel role for CK1 in cell adhesion dynamics.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cadherins are essential membrane proteins mediating cell-cell adhesion.
  • The dynamic regulation of cadherin-based cell-cell contacts is critical for physiological and pathological processes.
  • Molecular mechanisms governing cell-cell contact regulation remain incompletely understood.

Purpose of the Study:

  • To investigate the role of casein kinase 1 (CK1) in regulating cadherin-based cell-cell contacts.
  • To identify the specific mechanisms by which CK1 influences E-cadherin function.

Main Methods:

  • Utilized CK1 inhibitor (IC261) and CK1 overexpression to assess effects on cell-cell contacts.
  • Investigated CK1 localization relative to E-cadherin.
  • Performed in vitro and cell culture phosphorylation assays of E-cadherin by CK1.
  • Analyzed the impact of E-cadherin phosphorylation at serine 846 on its localization, adhesive activity, and beta-catenin interaction.

Main Results:

  • CK1 inhibition stabilized cadherin-based cell-cell contacts, whereas CK1 overexpression disrupted them.
  • CK1 was found to colocalize with E-cadherin and phosphorylate its cytoplasmic domain.
  • Serine 846 was identified as the major CK1 phosphorylation site on E-cadherin.
  • Phosphorylation of E-cadherin at S846 (S846D mutant) impaired its localization to cell-cell contacts, reduced adhesive activity, weakened beta-catenin interaction, and increased internalization.

Conclusions:

  • Casein kinase 1 (CK1) acts as a novel negative regulator of cadherin-based cell-cell contacts.
  • CK1-mediated phosphorylation of E-cadherin at serine 846 is a key mechanism for disrupting cell adhesion.

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