DDR1/E-cadherin complex regulates the activation of DDR1 and cell spreading

Chau-Zen Wang1, Yi-Chun Yeh, Ming-Jer Tang

  • 1Department of Physiology, Kaohsiung Medical University, Kaohsiung, Taiwan.

Insights

Epithelial (cell) cadherin (E-cadherin) negatively regulates discoidin domain receptor 1 (DDR1) activity and cell spreading by sequestering DDR1 at cell junctions, preventing collagen binding.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Discoidin domain receptors (DDRs) 1 and 2 are collagen receptors that control cell adhesion and behavior.
  • The adhesion-dependent regulation of DDR signaling pathways, particularly involving adhesion proteins, remains poorly understood.

Purpose of the Study:

  • To elucidate a novel mechanism of adhesion-dependent regulation of DDR1 signaling.
  • To investigate the cross-talk between DDR1 and E-cadherin in controlling cell adhesion and spreading.

Main Methods:

  • Utilized small interfering RNA (siRNA) to silence E-cadherin expression.
  • Investigated the formation of protein complexes between DDR1 and E-cadherin.
  • Assessed DDR1 activity and cell spreading in epithelial cells with and without E-cadherin.

Main Results:

  • E-cadherin forms complexes with DDR1 isoforms (a and b) independently of DDR1 activation and catenin binding.
  • E-cadherin negatively and adhesion-dependently regulates DDR1 activity and DDR1-suppressed cell spreading.
  • E-cadherin silencing restores DDR1 activity, DDR1-suppressed cell spreading, and DDR1 localization in epithelial cells.

Conclusions:

  • E-cadherin-mediated adhesions decrease DDR1 activity by sequestering DDR1 to cell junctions.
  • This sequestration prevents DDR1 interaction with its collagen ligand, thereby eliminating DDR1-suppressed cell spreading.
  • A novel cross-talk mechanism between DDR1 and E-cadherin regulates cell adhesion and behavior in epithelial cells.

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