Glycosphingolipid modification: structural diversity, functional and mechanistic integration of diabetes

Abstract

Glycosphingolipids (GSLs) are present in all mammalian cell plasma membranes and intracellular membrane structures. They are especially concentrated in plasma membrane lipid domains that are specialized for cell signaling. Plasma membranes have typical structures called rafts and caveola domain structures, with large amounts of sphingolipids, cholesterol, and sphingomyelin. GSLs are usually observed in many organs ubiquitously. However, GSLs, including over 400 derivatives, participate in diverse cellular functions. Several studies indicate that GSLs might have an effect on signal transduction related to insulin receptors and epidermal growth factor receptors. GSLs may modulate immune responses by transmitting signals from the exterior to the interior of the cell. Guillain-Barré syndrome is one of the autoimmune disorders characterized by symmetrical weakness in the muscles of the legs. The targets of the immune response are thought to be gangliosides, which are one group of GSLs. Other GSLs may serve as second messengers in several signaling pathways that are important to cell survival or programmed cell death. In the search for clear evidence that GSLs may play critical roles in various biological functions, many researchers have made genetically engineered mice. Before the era of gene manipulation, spontaneous animal models or chemical-induced disease models were used.

Keywords: Cell membrane; Diabetes mellitus; Glycosphingolipids; Mouse model.

Fig. 1

The synthetic pathway from ceramide. Following the synthesis of glucosylceramide, sphingomyelin, galactosylceramide, ceramide-1-phosphate, and sphingosine-1-phosphate, the derivatives are synthesized by enzyme activities predominantly in the Golgi apparatus.

Fig. 2

Illustration of a eukaryotic cell membrane. It composed of the lipid bilayer, consisting of hydrophobic tails and hydrophilic heads.

Fig. 3

Glycosphingolipids (GSLs), cholesterol, sphingomyelin, and glycoproteins present in the cell membrane. Some viruses and bacteria might catch and use these molecules as the entry gate into cells. Cell-cell interaction might also occur through these molecules.