Syndecan-4 deficiency impairs focal adhesion formation only under restricted conditions

Two domains of fibronectin deliver two different but cooperative signals re quired for focal adhesion formation. The signal from the cell-binding domai n is mediated by integrins, whereas the signal from the heparin-binding dom ain is recognized by heparan sulfate proteoglycans, of which syndecan-4 has been hypothesized to be involved in focal adhesion formation. We generated mice deficient in syndecan-4 to study its role directly. Even in fibroblas ts from syndecan-4-deficient mice, focal adhesions were formed, and actin f ibers terminated normally at focal adhesions when they were cultured on cov erslips coated with fibronectin or with a mixture of its cell-binding and h eparin-binding fragments. However, when the cells were cultured on the cell -binding fragment and the heparin-binding fragment was added to the medium, focal adhesion formation was impaired in the syndecan-4 null fibroblasts a s compared with that in wild-type cells. Therefore, syndecan-4 is essential for promoting focal adhesion formation only when the signal of the heparin -binding domain of fibronectin is delivered as a soluble form, most probabl y from the apical surface, When the signal is delivered as a substratum-bou nd form, other molecule(s) also participate(s) in the signal reception.