Cellular Biology of Gangliosides

Abstract

Sialic acid-containing glycosphingolipids, or gangliosides, are hybrid molecules composed of a hydrophilic sialyl oligosaccharide and a hydrophobic ceramide moiety, the latter consisting of a sphingoid base linked to a fatty acid. Though molecular species of the fatty acids and sphingosine in the ceramide component of gangliosides are heterogeneous, more significant heterogeneity is observed in the oligosaccharide moiety, which is primarily oriented exofacially in the cell surface, positionally advantaged to interact with neighboring cells and extra-cellular materials. In the animal kingdom, the lowest order in which gangliosides as well as sialic acids generally are detected is the Deuterostomia, in particular those more developed phylogenetically than the Echinodermata, but not those of the Prostomia (Hoshi and Nagai, 1975; Sugita et al., 1982; Wiegandt, 1985; Dennis et al., 1985), although recent subtle analysis has revealed that sialic acids and their polymeric form occur also in the insect Drosophila melanogaster (Roth et al., 1992). Thus, gangliosides seem to be concerned with evolutionarily acquired functions pertinent to higher animals. In vertebrates, they are ubiquitous constituents of all tissues and cells, and their oligosaccharide structures undergo alteration during cellular development, differentiation, ontogenesis, and aging, in keeping with their functional importance (Hakomori, 1990). In fact, by application of the monoclonal antibody technique, several gangliosides were shown to be the tumor-associated antigens, which are utilized as the target molecules for immunotherapy, as well as for the diagnosis of several tumors (Saleh et al., 1992).