Ezrin links syndecan-2 to the cytoskeleton

The syndecan family of heparan sulfate proteoglycans is known to associate with the actin cytoskeleton, possibly transducing signals from the extracel lular matrix. In the search for proteins that could mediate the association of syndecan-2 with the actin cytoskeleton we found that ezrin, a protein w hich links membrane receptors to the cytoskeleton, coimmunoprecipitated wit h syndecan-2 in COS-1 cells. In vitro assays indicated a direct association between the amino-terminal domain of ezrin and the cytoplasmic domain of s yndecan-2, Confocal microscopy showed colocalization of ezrin and syndecan- 2 in actin-rich microspikes in COS-1 cells. The syndecan-2/ezrin protein co mplex was resistant to 0.2% Triton X-100 extraction but the syndecan-2/amin o-terminal domain of ezrin complex was not, which indicated that carboxi-te rminal domain of ezrin is involved in the cytoskeleton anchorage of this pr otein complex. Additionally we observed that the activation of rhoA GTPase increased syndecan-2 insolubility in 0.2% Triton X-100 and syndecan-2/ezrin association, Taken together, these results indicate that ezrin connects sy ndecan-2 to the actin cytoskeleton.