Sci. STKE, 15 April 2003
PROTEOGLYCANS Heparan Sulfate Targeting of Syndecan-1
Cell-surface heparan sulfate proteoglycans bind to various extracellular proteins, including growth factors and proteases, and can thereby affect their function, increase their local concentration, and modify their interactions with receptors. In migrating plasma and myeloma cells, which become polarized, the transmembrane heparan sulfate proteoglycan syndecan-1 localizes to a membrane region called the uropod at the trailing edge of the cell. Syndecan-1 in the uropod plays a role in cell-cell and cell-extracellular matrix adhesion and may regulate the activity of heparin-binding cytokines and the bone destruction seen in myeloma. Yang et al. investigated the mechanism of syndecan-1 targeting to the uropod of myeloma cells and discovered that this was mediated by its heparan sulfate side chains and was regulated at the cell surface. Adding exogenous heparin (which structurally and functionally resembles heparan sulfate) to cultured myeloma cells or treating the cells with heparitinase to remove cell-surface heparan sulfate side chains triggered redistribution of immunofluorescently labeled syndecan-1 over the cell surface. Heparin-mediated redistribution was reversible; recovery was accelerated by antibody binding to syndecan-1 and was abolished by disruption of the actin cytoskeleton. Other heparan sulfate proteoglycans expressed in myeloma cells did not localize to the uropod. The authors expressed syndecan-1 mutants to determine that the heparan sulfate side chains were required for targeted localization, whereas the cytoplasmic and transmembrane regions were not. Thus, heparan sulfate side chains are not only important in mediating proteoglycan interactions with extracellular proteins, but may also play a role in cell-surface localization of proteoglycans.
Y. Yang, M. Børset, J. K. Langford, R. D. Sanderson, Heparan sulfate regulates targeting of syndecan-1 to a functional domain on the cell surface. J. Biol. Chem. 278, 12888-12893 (2003). [Abstract] [Full Text]
Citation: Heparan Sulfate Targeting of Syndecan-1. Sci. STKE 2003, tw150 (2003).
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