Functional roles of gangliosides in bio-signalling

Abstract

Brain gangliosides, a sialic acid-containing glycosphingolipid family enriched in brain, are discriminated from those of extra neural tissues by their characteristic structures of carbohydrate chain with large molecular diversity. Numerous minor components and monoclonal antibodies to them are useful to identify type, distribution and lineage of the cells, as shown in the recent finding of the ganglioside epitope of cholinergic neuron-specific Chol-1 antigens. Various cell biological effects of exogenous gangliosides (bioactive gangliosides) particularly with regard to cell growth and differentiation strongly suggest involvement of gangliosides and possibly their metabolic intermediates as second messenger in signaling pathways. The neuritogenic as well as synaptogenic effects of gangliosides may be interpreted by their action on protein kinases. The analysis of the neuritogenic activity of GQ1b ganglioside on human neuroblastoma cell lines strongly indicates the possibility that the action is carried out by coupling of GQ1b sugar-specific glycoreceptor of cell surface membrane and a unique, cell surface localized protein kinase (ecto-protein kinase) to phosphorylate cell surface proteins(s) with extracellular ATP. This cell surface (ecto) type of protein phosphorylation system which is in contrast to intracellular (endo) type of protein phosphorylation seems to highly develop in neuron. Possible involvement of gangliosides in synaptic function including ion-transport and long-term potentiation is also suggested.