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Vol. 20, Issue 4, 1141-1149, February 15, 2009

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A Shared Mechanism of Adhesion Modulation for Tenascin-C and Fibulin-1

Department of Molecular Biology, Princeton University, Princeton, NJ 08544

Submitted June 19, 2008; Revised November 14, 2008; Accepted December 10, 2008
Monitoring Editor: Mark H. Ginsberg

Adhesion modulatory proteins are important effectors of cell–matrix interactions during tissue remodeling and regeneration. They comprise a diverse group of matricellular proteins that confer antiadhesive properties to the extracellular matrix (ECM). We compared the inhibitory effects of two adhesion modulatory proteins, fibulin-1 and tenascin-C, both of which bind to the C-terminal heparin-binding (HepII) domain of fibronectin (FN) but are structurally distinct. Here, we report that, like tenascin-C, fibulin-1 inhibits fibroblast spreading and cell-mediated contraction of a fibrin–FN matrix. These proteins act by modulation of focal adhesion kinase and extracellular signal-regulated kinase signaling. The inhibitory effects were bypassed by lysophosphatidic acid, an activator of RhoA GTPase. Fibroblast response to fibulin-1, similar to tenascin-C, was dependent on expression of the heparan sulfate proteoglycan syndecan-4, which also binds to the HepII domain. Therefore, blockade of HepII-mediated signaling by competitive binding of fibulin-1 or tenascin-C represents a shared mechanism of adhesion modulation among disparate modulatory proteins.

* Present address: New York City College of Technology, City University of New York (CUNY), 300 Jay St., Brooklyn, NY 11201.

Address correspondence to: Jean Schwarzbauer (jschwarz{at}princeton.edu).