The role of glycosphingolipid metabolism in the developing brain

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. 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.

Ganglioside GD3 Enhances Invasiveness of Gliomas by Forming a Complex with Platelet-derived Growth Factor Receptor α and Yes Kinase

“…GD3 and GD2 are expressed mainly at early stages of development in the central nervous tissues in mice and other vertebrates. They become almost undetectable in few days postnatal (5). In turn, neuroectoderm-derived tumors such as neuroblastomas and melanomas and T-cell leukemias express ganglioside GD3 and/or GD2 that have been known as cancerassociated antigens (6,7).…”

Interaction of ganglioside GD3 with an EGF receptor sustains the self-renewal ability of mouse neural stem cells in vitro

“…G angliosides are ubiquitously expressed in all vertebrate cells and are particularly abundant in the nervous system (1). In early mammalian embryonic brain, the pattern of ganglioside expression is limited to simple gangliosides, predominantly GM3 (NeuAcα2-3Galβ1-4Glcβ1-1′Cer) and GD3 (NeuAcα2-8NeuAcα2-3Galβ1-4Glcβ1-1′Cer).…”

Multi-system disorders of glycosphingolipid and ganglioside metabolism

“…1 ). The type of sugars in the oligosaccharide backbone depends on the activity of glycosyltransferases in the Golgi, the cell type, and the developmental or disease stage (19)(20)(21)(22) ) (see below).…”