title: Thrombospondin-1-induced focal adhesion disassembly in fibroblasts requires Thy-1 surface expression, lipid raft integrity, and Src activation.
abstract: The hep I peptide of thrombospondin-1 is known to induce the disassembly of focal adhesions, a critical step in regulating cellular adhesive changes needed for cell motility. Fibroblasts that are heterogeneous with respect to the surface expression of Thy-1 differ markedly in morphology, cytoskeletal organization, and migration, suggesting differential regulation of focal adhesion dynamics. Here we demonstrate that disassembly of focal adhesions mediated by both full-length thrombospondin-1 and the hep I peptide in fibroblasts requires the expression of Thy-1, although it does not appear to function as a stable member of the hep I receptor complex. Consistent with a known function of Thy-1 in regulating lipid raft-associated signaling, intact lipid rafts are necessary for hep I-mediated focal adhesion disassembly. Furthermore, we establish Src family kinase (SFK) activation as a novel component required for hep I-induced signaling leading to focal adhesion disassembly. hep I induces transient phosphorylation of SFKs in Thy-1-expressing fibroblasts only. Therefore, we conclude that Thy-1 surface expression is required for thrombospondin-1-induced focal adhesion disassembly in fibroblasts through an SFK-dependent mechanism. This represents a novel role for Thy-1 in the regulation of fibroblast-matrix interactions critical to tissue homeostasis and remodeling.
authors.affiliation: Department of Biomedical Engineering, School of Engineering, University of Alabama at Birmingham, 35294, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Barker
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Pallero
authors.forename: Mark W
authors.initials: MW
authors.lastname: MacEwen
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Tilden
authors.forename: Anne
authors.initials: A
authors.lastname: Woods
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Murphy-Ullrich
authors.forename: James S
authors.initials: JS
authors.lastname: Hagood
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D022001:Focal Adhesions / Q000502:physiology*; D021962:Membrane Microdomains / Q000502:physiology; D051381:Rats; D015398:Signal Transduction; D019700:Thrombospondin 1 / Q000502:physiology*; D018800:Thy-1 Antigens / Q000096:biosynthesis*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D019700:Thrombospondin 1; D018800:Thy-1 Antigens; D019061:src-Family Kinases