Development regulation of ganglioside metabolism

Various reports have appeared indicating that the expression of gangliosides may be largely regulated at the genetic level. Evidence from analysis of the gene for this enzyme revealed binding sequences for a number of liver restricted transcription factors such as hepatocyte nuclear factor l a, liver specific factors D-binding protein (DBP), and liver enriched transcription activator protein (LAP), as well as the more general transcription factors AP-1 and AP-2. Presumably, the expression of the various glycosyltransferases for ganglioside synthesis may be regulated in an analogous manner. Factors involved in the regulation of ganglioside expression include the proper translocation and sorting of the glycolipid products in multi-glycosyltransferase systems. Disruption of the flow of gangliosides along their biosynthetic pathways also can cause alterations in ganglioside expression. It is demonstrated that polysialogangliosides exerted inhibitory effects feedback control. Another intriguing mechanism for the regulation of ganglioside synthesis states that in cultured cerebellar cells a shift in the biosynthesis from a- to b-series gangliosides occurred when the pH of the medium was lowered from 7.4 to 6.2, with the effect being reversible. Whether changes in pH occur in vivo to effect the shift in biosynthesis of gangliosides during development remains to be substantiated.