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Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
Published on: October 17, 2014
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.
Abstract:
Discoidin domain receptors (DDRs) 1 and 2, collagen receptors, regulate cell adhesion and a broad range of cell behavior. Their adhesion-dependent regulation of signaling associated with adhesion proteins has not been elucidated. We report a novel mechanism: the cross talk of DDR1 and E-cadherin negatively and adhesion dependently regulated both DDR1 activity and DDR1-suppressed cell spreading. E-cadherin forms complexes with both DDR1 isoforms (a and b). E-cadherin regulates DDR1 activity associated with the cell-junction complexes formed between DDR1 and E-cadherin. These complexes are formed independently of DDR1 activation and of beta-catenin and p120-catenin binding to E-cadherin; they are ubiquitous in epithelial cells. Small interfering RNA-mediated gene silencing of E-cadherin restores both DDR1 activity and DDR1-suppressed cell spreading and increases the apically and basally located DDR1 in E-cadherin-null cells. We conclude that E-cadherin-mediated adhesions decrease DDR1 activity, which subsequently eliminates DDR1-suppressed cell spreading, by sequestering DDR1 to cell junctions, which prevents its contact with collagen ligand.
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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