MOLECULAR ANALYSIS OF CELL-SURFACE BETA-1,4-GALACTOSYLTRANSFERASE FUNCTION DURING CELL-MIGRATION

Despite the identification and characterization of cell surface recept ors for the extracellular matrix, it is unknown how their relative exp ression and cytoskeletal association regulate cell migration. Previous studies have identified beta-1,4-galactosyltransferase (GalTase; EC 2 .4.1.38) on the surface of migrating cells, where it mediates cell mig ration on basal lamina matrices by associating with the cytoskeleton a nd binding to N-linked oligosaccharides in the E8 domain of laminin. I n this study, the function of GalTase during cell migration was examin ed directly by analyzing the migration rate of stably transfected cell lines in which the relative level of surface GalTase and its ability to associate with the cytoskeleton were altered. We show here that the cytoskeleton contains a limiting, saturable, number of binding sites for surface GalTase. Furthermore, the rate of cell migration was inver sely related to the ability of surface GalTase to associate with the c ytoskeleton. Elevating surface GalTase in excess of the number of cyto skeleton-binding sites reduced the rate of cell migration, whereas dec reasing the amount of surface GalTase available to bind the cytoskelet on increased migration rates. These results show that the rate of cell migration on basal lamina is directly dependent upon the expression o f surface GalTase and the ability of this protein to associate with a limiting number of cytoskeleton-binding sites.