If
the plug-in named ChemScape Chime is properly installed on
your computer, you should see a 3D GM3 molecule. The molecule can be moved
by clicking it with the left button of your mouse and its characteristics,
including automatic rotation, can be modified by clicking it with the right
button.
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download the plug-in:
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Free gangliosides bind fibroblast growth factor-2 (FGF2), thus preventing cell interaction and biological activity of the growth factor in endothelial cells. Here we investigated the role of cell-associated gangliosides in mediating the biological activity of FGF2.
Treatment of endothelial cells of different origin with the ganglioside biosynthesis inhibitors fumonisin B1, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, or D-1-threo-1-phenyl-2-hexa-decanoylamino-3-pyrrolidino-1-propanol-HCl impairs their capacity to proliferate when exposed to FGF2. Also, the mitogenic activity of FGF2 is inhibited by the GM1-binding cholera toxin B subunit (CTB). Conversely, overloading of endothelial GM 7373 cell membranes with exogenous GM1 causes a 10-fold increase of the mitogenic potency of FGF2.
125I-FGF2 binds to cell membrane GM1 (Kd = 3 nM) in complex ganglioside/heparan sulfate-deficient CHO-K1-pgsA745 cell mutants that were overloaded with exogenous GM1. Moreover, FGF2 competes with FITC-CTB for the binding to cell membrane GM1 in different CHO cell lines independently of their capacity to express heparan sulfate proteoglycans. Conversely, CTB inhibits cell proliferation triggered by FGF2 in CHO cells overexpressing the tyrosine kinase FGF receptor-1 (FGFR1). Finally, GM1-overloading confers to FGFR1-transfected, complex ganglioside-deficient CHO-K1 cell mutants the capacity to proliferate when stimulated by FGF2. This is inhibited by CTB.
Cell proliferation triggered by serum or by phorbol 12-myristate 13-acetate is instead independent of the cell membrane ganglioside milieu.
In
conclusion, cell membrane GM1 binds FGF2 and is required for the mitogenic
activity of the growth factor. This indicates that cell-associated gangliosides
may act as functional FGF2 co-receptors in different cell types.
Proc. Natl. Acad. Sci. USA
(2002) 99:4367-4372
Representative microphotographs of naïve CHO-K1 cells treated with FITC-CTB alone (a) and of GM1-overloaded CHO-K1 cells treated with FITC-CTB in the absence (b) or in the presence of a molar excess of unlabelled CTB (c) or FGF2 (d).