DDR1/E-cadherin complex regulates the activation of DDR1 and cell spreading.
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.
Wang
Chau-Zen
CZ
Department of Physiology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yeh
Yi-Chun
YC
Tang
Ming-Jer
MJ
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D007527:Isoenzymes; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D051176:beta Catenin; D020794:Receptor Protein-Tyrosine Kinases; D000095002:Delta Catenin; C000722347:CTNND1 protein, human