A role for syndecan-1 in coupling fascin spike formation by thrombospondin-1

An important role of cell matrix adhesion receptors is to mediate transmemb rane coupling between extracellular matrix attachment, actin reorganization . and cell spreading. Thrombospondin (TSP)-1 is a modulatory component of m atrix expressed during development, immune response, or wound repair. Cell adhesion to TSP-1 involves formation of biochemically distinct matrix conta cts based on stable fascin spikes. The cell surface adhesion receptors requ ired have not been identified, We report here that antibody clustering of s yndecan-1 proteoglycan specifically transduces organization of cortical act in and fascin bundles in several cell types. Transfection of COS-7 cells wi th syndecan-1 is sufficient to stimulate cell spreading, fascin spike assem bly, and extensive protrusive lateral ruffling on TSP-1 or on syndecan-1 an tibody. The underlying molecular mechanism depends on glycosaminoglycan (GA G) modification of the syndecan-l core protein at residues S45 or S47 for c ell membrane spreading and on the VC2 region of the cytoplasmic domain for spreading and fascin spike formation. Expression of the VC2 deletion mutant or GAG-negative syndecan-l showed that syndecan-1 is necessary in spreadin g and fascin spike formation by C2C12 cells on TSP-1, These results establi sh a novel role for syndecan-l protein in coupling a physiological matrix l igand to formation of a specific matrix contact structure.