Submitted on March 6, 2009
Revised on May 26, 2009
Accepted on May 26, 2009
DDR1/E-cadherin complex regulates the activation of DDR1 and cell spreading
Chau-Zen Wang1, Yi-Chun Yeh2, and Ming-Jer Tang3*
1 Kaohsiung Medical University
2 National Cheng-Kung University Medical College
3 National Cheng Kung University
* To whom correspondence should be addressed. E-mail: mjtang1{at}mail.ncku.edu.tw.
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 crosstalk 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 
-catenin and p120-catenin binding to E-cadherin; they are ubiquitous in epithelial cells. Small interfering RNA (siRNA)-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.
