Journal
JOURNAL OF CELL SCIENCE
Volume 121, Issue 10, Pages 1661-1670Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.020149
Keywords
PAI1; integrin; fibronectin; extracellular matrix; actin
Categories
Funding
- NCI NIH HHS [R01 CA058626, R56 CA058626, R56 CA058626-15A1, CA-58626] Funding Source: Medline
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The plasminogen activation system regulates matrix remodeling through both proteolytic and non-proteolytic mechanisms. Studies were undertaken to determine the effects of the plasminogen activator inhibitor 1 (PAI1) on the assembly of the fibronectin matrix. The addition of PAI1 to MG-63 cells caused a 1.5- to threefold increase in the rate of fibronectin matrix assembly which was associated with an increase in beta integrin activation. PAI1 treatment led to a marked decrease in focal contacts and stress fibers, whereas tensin-containing matrix contacts remained unaffected. The effects of PAI1 on matrix assembly were independent of both urokinase-type plasminogen activator (uPA) and urokinase-type plasminogen activator receptor (uPAR), indicating that the stimulation of matrix assembly by PAI1 does not depend on its anti-proteolytic activity or on the association of uPAR with integrin receptors. Antagonists of the alpha v beta 5 integrin mimicked the effect of PAI1 on cell morphology and fibronectin matrix deposition, indicating that stimulation of matrix assembly by PAI1 required disruption of the interaction between the alpha v beta 5 integrin and vitronectin. Consistent with this conclusion, the Q123K PAI1 mutant which does not bind vitronectin had no effect on matrix assembly. Our data identify PAI1 as a novel regulator of fibronectin matrix assembly, and indicate that this regulation occurs through a previously undescribed crosstalk between the alpha v beta 5 and alpha 5 beta 1 integrins.
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