Abstract
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.
Highlights
Glycosphingolipids (GSLs) are amphipathic lipids ubiquitously expressed in all vertebrate cells and body fluids, but they are especially abundant in the nervous system
Many studies have shown that the qualitative and quantitative changes in ganglioside expression in the nervous system correlate with certain cellular events during development
We focus on the metabolism and functional roles of GSLs, especially of gangliosides, in the developing brain
Summary
GSLs are primarily synthesized in the endoplasmic reticulum and matured in the Golgi apparatus by sequential addition of a single carbohydrate moiety to an existing acceptor lipid substrate [4]. Further addition of sialic acids by cytidine-5′-monophosphate (CMP)-sialic acid: GM3 a2-8 sialyltransferase (ST-II) and CMP-sialic acid: GD3 a2-8 sialyltransferase generates GD3 and GT3, respectively These simple gangliosides constitute the complex gangliosides belonging to the a-, b-, and c-series, respectively. In addition to elaboration of the carbohydrate chains, the ceramide components undergo considerably different expression patterns during development [11]. The shift of ganglioside patterns from simple to complex gangliosides is regulated primarily by the differential expression of glycogenes, namely glycosyltransferases. The increase of GalNAcT expression occurs in primary neural precursor cells during differentiation [9] These results suggest that a shift of ganglioside expression during development is regulated by changes of the expression level and activity of these key glycosyltransferases. Gangliosides and other GSLs, such as GalCer and sulfatide, present drastic pattern shifts during development. GalCer synthase (GalT-III) and sulfatide synthase genes are upregulated during oligodendrocyte differentiation and myelin formation [9] (Fig. 2C)
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