Tenascin-C suppresses Rho activation.
Cell binding to extracellular matrix (ECM) components changes cytoskeletal organization by the activation of Rho family GTPases. Tenascin-C, a developmentally regulated matrix protein, modulates cellular responses to other matrix proteins, such as fibronectin (FN). Here, we report that tenascin-C markedly altered cell phenotype on a three-dimensional fibrin matrix containing FN, resulting in suppression of actin stress fibers and induction of actin-rich filopodia. This distinct morphology was associated with complete suppression of the activation of RhoA, a small GTPase that induces actin stress fiber formation. Enforced activation of RhoA circumvented the effects of tenascin. Effects of active Rho were reversed by a Rho inhibitor C3 transferase. Suppression of GTPase activation allows tenascin-C expression to act as a regulatory switch to reverse the effects of adhesive proteins on Rho function. This represents a novel paradigm for the regulation of cytoskeletal organization by ECM.
Wenk
M B
MB
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA.
Midwood
K S
KS
Schwarzbauer
J E
JE
D016475:3T3 Cells; D000199:Actins / Q000502:physiology; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000502:physiology / Q000648:ultrastructure; D005337:Fibrin / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology / Q000648:ultrastructure; D005353:Fibronectins / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D051379:Mice; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D019063:Tenascin / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D011994:Recombinant Proteins; D019063:Tenascin; D005337:Fibrin; D020558:GTP Phosphohydrolases; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins