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.
Wu
C
C
Department of Biochemistry and Molecular Biology, Samuel C. Johnson Medical Research Center, Mayo Clinic Scottsdale, AZ 85259, USA.
Hughes
P E
PE
Ginsberg
M H
MH
McDonald
J A
JA
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D005109:Extracellular Matrix / Q000648:ultrastructure*; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D039564:Integrin alphaV; D039661:Integrin beta3; D046911:Macromolecular Substances; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D017469:Receptors, Fibronectin / Q000502:physiology*; D011994:Recombinant Proteins
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D005353:Fibronectins; D039564:Integrin alphaV; D039661:Integrin beta3; D046911:Macromolecular Substances; D010980:Platelet Membrane Glycoproteins; D017469:Receptors, Fibronectin; D011994:Recombinant Proteins