Characterization of syntenin, a syndecan-binding PDZ protein, as a component of cell adhesion sites and microfilaments

Syntenin is a PDZ protein that binds the cytoplasmic C-terminal FYA motif o f the syndecans. Syntenin is widely expressed. In cell fractionation experi ments, syntenin partitions between the cytosol and microsomes. Immunofluore scence microscopy localizes endogenous and epitope-tagged syntenin to cell adhesion sites, microfilaments, and the nucleus. Syntenin is composed of at least three domains. Both PDZ domains of syntenin are necessary to target reporter tags to the plasma membrane. The addition of a segment of 10 amino acids from the N-terminal domain of syntenin to these PDZ domains increase s the localization of the tags to stress fibers and induces the formation o f long, branching plasma membrane extensions. The addition of the complete N-terminal region, in contrast, reduces the localization of the tags to pla sma membrane/adhesion sites and stress fibers, and reduces the morphotypica l effects. Recombinant domains of syntenin with the highest plasma membrane localization display the lowest nuclear localization. Syndecan-1, E-cadher in, beta -catenin, and alpha -catenin colocalize with syntenin at cell-cell contacts in epithelial cells, and coimmunoprecipitate with syntenin from e xtracts of these cells. These results suggest a role for syntenin in the co mposition of adherens junctions and the regulation of plasma membrane dynam ics, and imply a potential role for syntenin in nuclear processes.