DIFFERENTIAL MODULATION OF BASIC FIBROBLAST AND EPIDERMAL GROWTH-FACTOR RECEPTOR ACTIVATION BY GANGLIOSIDE GM3 IN CULTURED RETINAL MULLER GLIA

Polypeptide growth factors and membrane-bound gangliosides are involve d in cell signaling, including that observed in cells of neural origin , To analyze possible interactions between these two systems, we inves tigated the modulation of short- and long-term responses to basic fibr oblast and epidermal growth factor (bFGF and EGF, respectively) in cul tured retinal Muller glial cells following experimental modification o f their ganglioside composition, These glial cells readily incorporate d exogenously administered GM3 ganglioside, which was not substantiall y metabolized within 24 h, Such treatments significantly inhibited bFG F-induced DNA replication and cell migration, while having much less e ffect on analogous EGF-mediated behaviors, To explore GM3/growth facto r interactions further, different aspects of glial metabolism in respo nse to bFGF or EGF stimulation were examined: membrane fluidity, growt h factor binding, global and individual changes in growth factor-induc ed phosphotyrosine levels, and growth factor-induced activation of mit ogen-activated protein kinase. GM3 reduced the intensity of immunocyto chemical labeling of phosphotyrosine-containing proteins within bFGF-s timulated cells and down-regulated FGF receptor activation and tyrosin e phosphorylation of its cellular substrates, whereas similar paramete rs in EGF-stimulated cells were much less affected. Hence the data rev eal a complex relationship in normal neural cells between polypeptide growth factors and membrane-bound gangliosides, which may participate in retinal cellular physiology in vivo. (C) 1996 Wiley-Liss, Inc.