Biosynthesis and Function of Gangliosides: Gangliosides appear to participate in the transmission of membrane-mediated information.

Abstract

Gangliosides are unique acidic glycolipids that are selectively concentrated in the plasma membrane of cells. Surface labeling studies have demonstrated that at least a portion of the oligosaccharide chain of gangliosides extends beyond the hydrophobic region of the cell membrane, whereas the lipid moiety of gangliosides (ceramide) is imbedded in the membrane bilayer. It is becoming increasingly apparent that gangliosides participate in the internalization of environmental signals elicited by cholera toxin and glycoprotein hormones such as thyrotropic hormone and chorionic gonadotropin as well as other substances such as interferon and possibly serotonin. The mechanism by which cholera toxin binds to a specific ganglioside receptor on the cell surface and subsequently activates adenylate cyclase provides a model for the interaction of trophic agents with gangliosides. We would predict that analogous phenomena involving gangliosides will be discovered in brain. The biosynthesis of gangliosides proceeds by the ordered sequential addition of sugars to the lipid moiety. These reactions are catalyzed by a cluster of membrane-bound glycosyltransferases. Any alteration in the activity or specificity of one of these enzymes will result in a dramatic change in the ganglioside pattern of an afflicted cell or organ. The drastic consequences that accompany abnormalities of ganglioside synthesis have been documented in a heritable metabolic disorder in vivo and in tumorigenic transformation of cells in vitro. In this article, we have attempted to unify these observations and to provide a reasonable interpretation of the role of gangliosides in mediating cell surface phenomena.