Identification of a new biological function for the integrin alpha(v)beta(3): Initiation of fibronectin matrix assembly

Fibronectin matrix assembly is a complex cellular process initiated by specific fibronectin-binding cell surface receptors. Although the integrin alpha(5) beta(1) has been implicated in the assembly of fibronectin matrices, fibroblastic cells derived from alpha(5) integrin null mutant embryos assemble a fibronectin matrix. Thus, alternative receptors must support this process. Although the platelet integrin alpha(IIb)beta(3) supports fibronectin matrix assembly, its expression is restricted to platelets. We report that alpha(v) beta(3) integrin, a fibronectin receptor expressed on many cell types provides an alternative pathway for the assembly of soluble fibronectin into the extracellular matrix. This process occurs independent of alpha(5) beta(1), is also modulated by activation, and the resulting matrix is biochemically indistinguishable from that assembled under the control of alpha(5) beta(1). Matrix assembly requires binding to the RGD site in the 10th type III repeat of fibronectin, as well as the participation of the amino-terminal matrix assembly domain. The participation of two distinct integrins in fibronectin matrix assembly suggests a model for the involvement of integrins in a dual system of extracellular matrix assembly and recognition controlled by intracellular activation of extracellular receptors.