Heparin II Domain of Fibronectin Uses α4β1 Integrin to Control Focal Adhesion and Stress Fiber Formation, Independent of Syndecan-4

• Published in: The Journal of biological chemistry 2005-02, Vol.280 (8), p.6915-6922
• Main Authors: Peterson, Jennifer A., Sheibani, Nader, David, Guido, Garcia-Pardo, Angeles, Peters, Donna M.
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M406625200

Co-signaling events between integrins and cell surface proteoglycans play a critical role in the organization of the cytoskeleton and adhesion forces of cells. These processes, which appear to be responsible for maintaining intraocular pressure in the human eye, involve a novel cooperative co-signaling pathway between α5β1 and α4β1 integrins and are independent of heparan sulfate proteoglycans. Human trabecular meshwork cells isolated from the eye were plated on type III 7–10 repeats of fibronectin (α5β1 ligand) in the absence or presence of the heparin (Hep) II domain of fibronectin. In the absence of the Hep II domain, cells had a bipolar morphology with few focal adhesions and stress fibers. The addition of the Hep II domain increased cell spreading and the numbers of focal adhesions and stress fibers. Cell spreading and stress fiber formation were not mediated by heparan sulfate proteoglycans because treatment with chlorate, heparinase, or soluble heparin did not prevent Hep II domain-mediated cell spreading. Cell spreading and stress fiber formation were mediated by α4β1 integrin because soluble anti-α4 integrin antibodies inhibited Hep II domain-mediated cell spreading and soluble vascular cell adhesion molecule-1 (α4β1 ligand)-induced cell spreading. This is the first demonstration of the Hep II domain mediating cell spreading and stress fiber formation through α4β1 integrin. This novel pathway demonstrates a cooperative, rather than antagonistic, role between α5β1 and α4β1 integrins and suggests that interactions between the Hep II domain and α4β1 integrin could modulate the strength of cytoskeleton-mediated processes in the trabecular meshwork of the human eye.