title: Molecular analysis of cell surface beta-1,4-galactosyltransferase function during cell migration.
abstract: Despite the identification and characterization of cell surface receptors for the extracellular matrix, it is unknown how their relative expression 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 migration on basal lamina matrices by associating with the cytoskeleton and binding to N-linked oligosaccharides in the E8 domain of laminin. In this study, the function of GalTase during cell migration was examined 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 inversely related to the ability of surface GalTase to associate with the cytoskeleton. Elevating surface GalTase in excess of the number of cytoskeleton-binding sites reduced the rate of cell migration, whereas decreasing the amount of surface GalTase available to bind the cytoskeleton increased migration rates. These results show that the rate of cell migration on basal lamina is directly dependent upon the expression of surface GalTase and the ability of this protein to associate with a limiting number of cytoskeleton-binding sites.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: P A
authors.initials: PA
authors.lastname: Appeddu
authors.forename: B D
authors.initials: BD
authors.lastname: Shur
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D051379:Mice; D009237:N-Acetyllactosamine Synthase / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D014162:Transfection
chemical_list: D009237:N-Acetyllactosamine Synthase