Biosynthesis and Function of Gangliosides

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 oligosaccharde chain of gangliosides extends beyond the hydrophe) 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 celraction of trophic agents with gangliosides. We would predict that analyogous 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.