Integrin-syndecan cooperation governs the assembly of signalling complexes during cell spreading

Cell adhesion to fibronectin (FN) triggers the formation and maturation of adhesion complexes by modulating the activity of the Rho family of GTPases. Cells plated onto a ligand of integrin α5β1 spread but fail to form focal adhesions or fully organize actin into bundled stress fibres unless co-stimulated with a ligand of syndecan 4. Engagement of syndecan 4 in such pre-spread cells recapitulates the Rac1 and RhoA activation profiles observed during spreading on whole FN. Furthermore, since adhesion to a ligand of α5β1 alone does not activate Rac1, engagement of syndecan 4 appears to be an absolute requirement. In related work, we have examined differences in the mechanism of focal adhesion formation mediated by the FN-binding integrins α4β1 and α5β1. Two signalling differences were found. First, while α5β1 required syndecan 4 as a co-receptor, α4β1 did not. Second, focal adhesion formation via α5β1 required PKCα activation, but only basal PKCα activity was observed following adhesion via α4β1. These findings demonstrate that different integrins can signal to induce focal adhesion formation by different mechanisms. Copyright © Novartis Foundation 2005.