Syndecan proteoglycan contributions to cytoskeletal organization and contractility

Cells exert tension on the extracellular matrix through specific receptors that link to the actin cytoskeleton. The best characterized are the integrins, which, when activated and clustered, can link to the extracellular matrix at specialized adhesion zones, known as focal contacts or focal adhesions. However, other transmembrane receptors can also localize there, including one transmembrane proteoglycan, syndecan-4. This heparan sulfate proteoglycan can also link directly to the cytoskeleton through alpha-actinin, and can signal through protein kinase C. In turn, the pathway leads to RhoA and Rho kinases that control actomyosin contractility. Syndecan-4 may, therefore, be a sensor of tension exerted on the matrix. These processes are described here, their significance being potential roles in wound contraction, tumor-stroma interactions, fibrosis and the regulation of motility.