No abstract

Gangliosides are sialic acid-containing glycosphingolipids that are most abundant in the nervous system. Heterogeneity and diversity of the structures in their carbohydrate chains are characteristic hallmarks of these lipids; so far, 188 gangliosides with different carbohydrate structures have been identified in vertebrates. The molecular structural complexity increases manifold if one considers heterogeneity in the lipophilic components. The expression levels and patterns of brain gangliosides are known to change drastically during development. In cells, gangliosides are primarily, but not exclusively, localized in the outer leaflets of plasma membranes and are integral components of cell surface microdomains with sphingomyelin and cholesterol from which they participate in cell-cell recognition, adhesion, and signal transduction. In this brief review, we discuss the structures, metabolism and functions of gangliosides.

Gangliosides are expressed in the outer leaflet of the plasma membrane of the cells of all vertebrates and are particularly abundant in the nervous system. Ganglioside metabolism is closely associated with the pathology of

Glycosphingolipids (GSLs) and their sialic acid-containing derivatives, gangliosides, are important cellular components and are abundant in the nervous system. They are known to undergo dramatic changes during brain development. However, knowledge on the mechanisms underlying their qualitative and qualitative changes is still fragmentary. In this investigation, we have provided a detailed study on the developmental changes of the expression patterns of GSLs, GM3, GM1, GD3, GD1a, GD2, GD1b, GT1b, GQ1b, A2B5 antigens (c-series gangliosides such as GT3 and GQ1c), Chol-1a (GT1aa and GQ1ba), glucosylceramide, galactosylceramide (O1 antigen), sulfatide (O4 antigen), stage-specific embryonic antigen-1 (Lewis x) glycolipids, and human natural killer-1 glycolipid (sulfoglucuronosyl paragloboside) in developing mouse brains [embryonic day 12 (E12) to adult]. In E12-E14 brains, GD3 was a predominant ganglioside. After E16, the concentrations of GD3 and GM3 markedly decreased, and the concentrations of a-series gangliosides, such as GD1a, increased. GT3, glucosylceramide, and stagespecific embryonic antigen-1 were expressed in embryonic brains. Human natural killer-1 glycolipid was expressed transiently in embryonic brains. On the other hand, Chol-1a, galactosylceramide, and sulfatide were exclusively found after birth. To provide a better understanding of the metabolic basis for these changes, we analyzed glycogene expression patterns in the developing brains and found that GSL expression is regulated primarily by glycosyltransferases, and not by glycosidases. In parallel studies using primary neural precursor cells in culture as a tool for studying developmental events, dramatic changes in ganglioside and glycosyltransferase gene expression were also detected in neurons induced to differentiate from neural precursor cells, including the expression of GD3, followed by up-regulation of complex a-and b-series gangliosides. These changes in cell culture systems resemble that occurring in brain. We conclude that the dramatic changes in GSL pattern and content can serve as useful markers in neural development and that these changes are regulated primarily at the level of glycosyltransferase gene expression.

Glycosphingolipids (GSLs) are amphipathic lipids ubiquitously expressed in all vertebrate cells and body fluids, but they are especially abundant in the nervous system. The synthesis of GSLs generally is initiated in the endoplasmic reticulum and completed in the Golgi apparatus, followed by transportation to the plasma membrane surface as an integral component. The amount and expression patterns of GSLs change drastically in brains during the embryonic to postnatal stages. Recent studies have revealed that GSLs are highly localized in cell surface microdomains and function as important components that mediate signal transduction and cell adhesion. Also in developing brains, GSLs are suggested to play important roles in nervous system formation. Disturbance of GSL expression and metabolism affects brain function, resulting in a variety of diseases, particularly lysosomal storage diseases. In this review, we describe some aspects of the roles of GSLs, especially of gangliosides, in brain development. Glycosphingolipids (GSLs) are amphipathic molecules composed of a hydrophilic carbohydrate chain and a hydrophobic ceramide moiety that contains a sphingosine and a FA residue (1). GSLs containing one or more sialic acid residues in the carbohydrate chain are referred to as gangliosides. Based on the sequences of the core carbohydrate residues, GSLs are classified into a number of series, including gala-, ganglio-, isoganglio-, lacto-, neolacto-, lactoganglio-, globo-, isoglobo-, and muco-series.