title: Discoidin Domain Receptor 1 Mediates Myosin-Dependent Collagen Contraction.
abstract: Discoidin domain receptor 1 (DDR1) is a tyrosine kinase collagen adhesion receptor that mediates cell migration through association with non-muscle myosin IIA (NMIIA). Because DDR1 is implicated in cancer fibrosis, we hypothesized that DDR1 interacts with NMIIA to enable collagen compaction by traction forces. Mechanical splinting of rat dermal wounds increased DDR1 expression and collagen alignment. In periodontal ligament of DDR1 knockout mice, collagen mechanical reorganization was reduced >30%. Similarly, cultured cells with DDR1 knockdown or expressing kinase-deficient DDR1d showed 50% reduction of aligned collagen. Tractional remodeling of collagen was dependent on DDR1 clustering, activation, and interaction of the DDR1 C-terminal kinase domain with NMIIA filaments. Collagen remodeling by traction forces, DDR1 tyrosine phosphorylation, and myosin light chain phosphorylation were increased on stiff versus soft substrates. Thus, DDR1 clustering, activation, and interaction with NMIIA filaments enhance the collagen tractional remodeling that is important for collagen compaction in fibrosis.
authors.affiliation: Matrix Dynamics Group, University of Toronto, Toronto, ON M5S 3E2, Canada. Electronic address: nuno.coelho@utoronto.ca.
authors.forename: Nuno M
authors.initials: NM
authors.lastname: Coelho
authors.affiliation: Matrix Dynamics Group, University of Toronto, Toronto, ON M5S 3E2, Canada.
authors.forename: Pamma D
authors.initials: PD
authors.lastname: Arora
authors.affiliation: Matrix Dynamics Group, University of Toronto, Toronto, ON M5S 3E2, Canada.
authors.forename: Sander
authors.initials: S
authors.lastname: van Putten
authors.affiliation: Matrix Dynamics Group, University of Toronto, Toronto, ON M5S 3E2, Canada.
authors.forename: Stellar
authors.initials: S
authors.lastname: Boo
authors.affiliation: Matrix Dynamics Group, University of Toronto, Toronto, ON M5S 3E2, Canada.
authors.forename: Petar
authors.initials: P
authors.lastname: Petrovic
authors.affiliation: Matrix Dynamics Group, University of Toronto, Toronto, ON M5S 3E2, Canada.
authors.forename: Alyna Xue
authors.initials: AX
authors.lastname: Lin
authors.affiliation: Matrix Dynamics Group, University of Toronto, Toronto, ON M5S 3E2, Canada.
authors.forename: Boris
authors.initials: B
authors.lastname: Hinz
authors.affiliation: Matrix Dynamics Group, University of Toronto, Toronto, ON M5S 3E2, Canada.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: McCulloch
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003094:Collagen / Q000378:metabolism*; D000070819:Discoidin Domain Receptor 1 / Q000378:metabolism*; D005260:Female; D005355:Fibrosis / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018995:Myosin Heavy Chains / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism
chemical_list: D018994:Myosin Light Chains; D003094:Collagen; C511169:DDR1 protein, rat; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases; D018995:Myosin Heavy Chains
keywords: DDR1; collagen remodeling; contraction; myosin