Integrin activation and cytoskeletal interaction are essential for the assembly of a fibronectin matrix.
Fibronectin (Fn) matrices are vital to vertebrate development and wound healing and modulate tumorigenesis. We used a recombinant Fn-binding integrin alpha IIb beta3, to define rules for integrin-initiated Fn matrix formation. We report the following. First, multiple Fn-binding integrins can support matrix assembly; their activation state controls fibrillogenesis. Second, Fn binding to cells expressing an activated integrin is necessary but not sufficient for matrix assembly. Additional "postoccupancy" events involving the integrin beta, but not the alpha subunit, cytoplasmic domain are needed. Third, these postoccupancy events require an intact actin cytoskeleton. We propose a model for integrin involvement in Fn fibrillogenesis that reconciles previous paradoxes and suggests novel approaches to the therapeutic control of Fn matrix assembly.
Department of Biochemistry and Molecular Biology Mayo Clinic Scottsdale, Arizona 85239, USA.
C
C
Wu
V M
VM
Keivens
T E
TE
O'Toole
J A
JA
McDonald
M H
MH
Ginsberg
D000199:Actins / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D004220:Disulfides / Q000032:analysis; D004229:Dithiothreitol; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics / Q000378:metabolism*; D017469:Receptors, Fibronectin / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D017384:Sequence Deletion; D013439:Sulfhydryl Reagents
D000199:Actins; D004220:Disulfides; D005353:Fibronectins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017469:Receptors, Fibronectin; D011993:Recombinant Fusion Proteins; D013439:Sulfhydryl Reagents; D015638:Cytochalasin D; D004229:Dithiothreitol