title: The collagen receptor DDR1 regulates cell spreading and motility by associating with myosin IIA.
abstract: The spreading and migration of cells on adhesive substrates is regulated by the counterbalance of contractile and protrusive forces. Non-muscle myosin IIA, an ubiquitously expressed contractile protein and enzyme, is implicated in the regulation of cell spreading and directional migration in response to various stimuli. Here we show that discoidin domain receptor 1 (DDR1), a tyrosine kinase receptor activated by type I collagen, associates with the non-muscle myosin IIA heavy chain (NMHC-IIA) upon ligand stimulation. An association was also indicated by coimmunoprecipitation of NMHC-IIA with full-length DDR1, but not with the truncated DDR1d-isoform lacking the kinase domain. DDR1 was important for assembly of NMHC-IIA into filaments on cells plated on collagen. DDR1 expression inhibited cell spreading over collagen but promoted cell migration. By contrast, blockade of non-muscle myosin II activity by blebbistatin enhanced cell spreading but inhibited migration over collagen. We propose that myosin and DDR1 impact cell spreading and migration by regulating adhesive contacts with collagen.
authors.affiliation: Department of Laboratory Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.forename: Pamela
authors.initials: P
authors.lastname: Arora
authors.forename: Christopher A
authors.initials: CA
authors.lastname: McCulloch
authors.forename: Wolfgang F
authors.initials: WF
authors.lastname: Vogel
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D000070819:Discoidin Domain Receptor 1; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D024507:Nonmuscle Myosin Type IIA / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D024042:Collagen Type I; D006576:Heterocyclic Compounds, 4 or More Rings; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; C525088:Myh9 protein, mouse; C472645:blebbistatin; C092030:DDR1 protein, human; C083249:Ddr1 protein, mouse; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains