Ganglioside cells

Glycosphingolipids are constituents of the outer leaflet of plasma membranes and are important in cell adhesion and cell recognition. Some are antigens, eg, ABO blood group substances. Certain gangliosides function as receptors for bacterial toxins (eg, for cholera toxin, which subsequently activates adenylyl cyclase). 

The glycosphingolipids (GSLs) are sugar-containing lipids built on a backbone of ceramide they include galactosyl- and glucosylceramide (cerebrosides) and the gangliosides. Their structures are described in Chapter 14. They are mainly located in the plasma membranes of cells. 

In this context, divalent presentation of this promising candidate has been investigated by the authors using the fixed cone conformation of calix[4]arene to allow introduction of the molecules onto the upper rim, and their projection into the same portion of space, thus mimicking, to some extent, a small portion of the natural cell-surface ganglioside. The synthesis of the divalent neoglycoconjugate was based on initial functionalization of the corresponding diacid with an aminated spacer and further introduction of squaric acid moieties. 

Simons, M., Friedrichson, T., Schulz, J.B., Pitto, M., Masserini, M., and Kurzchalia, T.V. (1999) Exogenous administration of gangliosides displaces GPI-anchored proteins from lipid microdomains in living cells. Mol. Biol. Cell 10, 3187-3196. 

Spiegel, S., Yamada, K.M., Horn, B.E., Moss, J., and Fishman, P.FL (1985) Fluorescent gangliosides as probes for the retention and organization of fibronectin by ganglioside-deficient mouse cells. /. Cell Biol. 100, 721-726. 

Because membranes components participate in nearly every cell activity their structures are also dynamic and far from the equilibrium states that are most readily understood in biophysical terms. Newly synthesized bilayer lipids are initially associated with endoplasmic reticulum (Ch.3) whereas phospholipids initially insert into the cytoplasmic leaflet while cholesterol and sphingolipids insert into the luminal endoplasmic reticulum (ER) leaflet. Glycosylation of ceramides occurs as they transit the Golgi compartments, forming cerebrosides and gangliosides in the luminal leaflet. Thus, unlike model systems, the leaflets of ER membranes are asymmetric by virtue of their mode of biosynthesis. 

The initial step in the sequence of events leading to influenza virus infections in mammalian hosts is mediated by the multiple attachment of virus particles to host sialoside receptors in the nasopharynx [41]. These receptors consist largely of cell surface sialylated glycoproteins and gangliosides. The subsequent steps involve receptor-mediated endocytosis with ensuing release of the viral nucleo-plasmid. The first event responsible for the receptor-virus interaction is therefore an attractive target for both antiviral and related microbial intervention. 

Among the important glycolipids, which are combinations of carbohydrate and lipid, are the cerebrosides and gangliosides. These are constituents of brain and nervous tissue and are usually considered with lipids because they are water-insoluble. Water-soluble polymers of high relative molecular mass containing lipid and carbohydrate, known as lipopolysaccharides, are found in bacterial cell walls. 

A. A. Wolf, M. G. Jobling, S. Wimer-Mackin, M. Ferguson-Maltzman, J. L. Madara, R. K. Holmes, and W. I. Lencer. Ganglioside structure dictates signal transduction by cholera toxin and association with caveolae-like membrane domains in polarized epithelia. J Cell Biol. 141 917-927 (1998). 

Hanai, N., Dohi, T., Nores, G. A., and Hakomori, S. (1988). A novel ganglioside, de-N-acetyl-GM3 (II3NeuNH2LacCer), acting as a strong promoter for epidermal growth factor receptor kinase and as a stimulator for cell growth. /. Biol. Chem. 263, 6296-6301. 

Gangliosides are a class of glycosphingolipid characterized by the presence of one or more sialic acid residues. They are located in the cell membranes, particularly in the plasma membrane, of almost all cell types. They are anchored in the membranes through their ceramide moiety and have the polar sugar-containing group in the extracytoplasmic side. They are particularly abundant in the nervous system where their expression pattern is modulated during development. 

It was also demonstrated that ceramides derived from sphingomyelin breakdown mediated by ASM are used for ganglioside biosynthesis, up to the generation of GD3. Indeed, lymphoblastoid cells derived from Niemann-... 

Goins B, Ligler FS, Rudolph AS. Inclusion of ganglioside GMl into liposome encapsulated hemoglobin does not extend circulation persistence at clinically relevant doses. Artif Cells Blood Substit Immobil Biotechnol 1994 22 9. 

Caveolae can mediate the delivery of CtxB that binds to GM1 ganglioside at the plasma membrane and is delivered to intracellular compartments. Cholera toxin, produced by Vibrio cholerae, consists of five identical subunits B and one A chain. In addition to labeled SV40 and caveolin-1-GFP, CtxB is one of the most commonly used caveolae markers. However, two groups reported that the toxin is internalized by either a clathrin-independent caveolae pathway or a clathrin-dependent uptake, bringing its selectivity/specificity into question (31,81,118). We controlled the suitability of this marker for COS-7 cells pretreated with CPZ, mpCD, and filipin and as expected, the uptake was not influenced by CPZ treatment but was strongly decreased by the latter two (data not shown). 

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