Syndecan-4 is a widely expressed transmembrane heparan sulfate proteoglycan which localizes to focal adhesions. Previous studies showed that the syndecan-4 cytoplasmic domain can associate with and potentiate the activity of protein kinase C, which is required for focal adhesion formation. To examine further the role of syndecan-4 in cell adhesion, we expressed syndecan-4 cDNA constructs in CHO-K1 cells. Syndecan-2 transfection was used to confirm effects seen were specific for syndecan-4. Cells overexpressing full length syndecan-4 core protein exhibited a more flattened, fibroblastic morphology, with increased focal adhesion formation and decreased cell motility. Expression of a syndecan-4 core protein with either a partial or complete deletion of the cytoplasmic domain or of an antisense construct led to markedly decreased spreading and focal adhesion formation, a more epithelioid morphology, and decreased motility. Overexpression of syndecan-2 changed the adhesive phenotype, but did not markedly alter focal adhesion and microfilament bundle formation. The data suggest that syndecan-4 is a regulator of focal adhesion and stress fiber formation, and influences both morphology and migration.
Keywords: Amino Acid Sequence; Animals; CHO Cells; Cell Adhesion; Cell Division; Cell Size; Chemotaxis; Cricetinae; Cytoskeleton; Epithelial Cells; Flow Cytometry; Liver; Membrane Glycoproteins; Molecular Sequence Data; Mutagenesis; Protein Kinase C; Proteoglycans; Rats; Recombinant Proteins; Sequence Deletion; Sequence Homology, Amino Acid; Syndecan-2; Syndecan-4; Transfection