ACTIN CYTOSKELETON OF FIBROBLASTS ORGANIZES SURFACE PROTEOGLYCANS THAT BIND BASIC FIBROBLAST GROWTH-FACTOR AND LIPOPROTEIN-LIPASE

Cell surface proteoglycans participate in molecular events that regula te cell adhesion, migration, and proliferation. To investigate the org anization of these molecules at the cell surface, the distribution of two well-known proteoglycan ligands has been studied. These ligands, l ipoprotein lipase and basic fibroblast growth factor, showed a charact eristic binding pattern consisting of highly organized parallel arrays that crossed the upper surface of human skin fibroblasts. The proteog lycan nature of the binding sites was evident from their susceptibilit y to heparinases, and from ligand displacement by heparin. Parallel lo calization of the ligands and actin, and treatment of the cells with c ytochalasin, showed that the binding proteoglycans are organized by th e actin cytoskeleton. The ligands induced a different behaviour of the binding sites on incubation of the cells at 37 degrees C. Lipoprotein lipase produced a movement of the binding proteoglycans along the act in filaments towards the cell center. In contrast, after binding of ba sic fibroblast growth factor the binding proteoglycans remained spread over the cell surface and actin depolymerization was induced. Since a n increasing number of ligands appear to depend on proteoglycans for t heir interactions with their high affinity receptors, distribution and movement of proteoglycans at the cell surface that is organized by th e actin cytoskeleton could direct and enhance the encounters between t he ligands and their specific receptors. (C) 1995 Wiley-Liss, Inc.