Thrombospondin-1-induced focal adhesion disassembly in fibroblasts requires Thy-1 surface expression, lipid raft integrity, and Src activation.
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.
Barker
Thomas H
TH
Department of Biomedical Engineering, School of Engineering, University of Alabama at Birmingham, 35294, USA.
Pallero
Manuel A
MA
MacEwen
Mark W
MW
Tilden
Samuel G
SG
Woods
Anne
A
Murphy-Ullrich
Joanne E
JE
Hagood
James S
JS
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
D019700:Thrombospondin 1; D018800:Thy-1 Antigens; D019061:src-Family Kinases