Identification of a New Biological Function for the Integrin α_vβ₃: Initiation of Fibronectin Matrix Assembly

Abstract

Fibronectin matrix assembly is a complex cellular process initiated by specific fibronectin-binding cell surface receptors. Although the integrin α₅β₁ has been implicated in the assembly of fibronectin matrices, fibroblastic cells derived from α₅ integrin null mutant embryos assemble a fibronectin matrix. Thus, alternative receptors must support this process. Al though the platelet integrin α_IIbβ₃ supports fibronectin matrix assembly, its expression is restricted to platelets. We report that α_vβ₃ 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 α₅β₁, is also modulated by activation, and the resulting matrix is biochemically indistinguishable from that assembled under the control of α₅β₁. 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.

Key Words:

• Integrins
• Fibronectin
• Matrix Assembly