Tenascin-C suppresses Rho activation.

Journal article

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.

Authors: Wenk, M; Midwood, K; Schwarzbauer, J

• Journal: Journal of cell biology
• Volume: 150
• Issue: 4
• Pages: 913-920
• Publication date: 2000-08-01
• DOI: 10.1083/jcb.150.4.913
• EISSN: 1540-8140
• ISSN: 0021-9525
• Language: English
• Keywords: 3T3 Cells; Fibroblasts; Substrate Specificity; Extracellular Matrix Proteins; Recombinant Proteins; Fibronectins; Cell Adhesion; cdc42 GTP-Binding Protein; rho GTP-Binding Proteins; GTP Phosphohydrolases; Fibrin; Actins; Rats; Tenascin; Mice; Animals; Cytoskeleton