Gangliosides cholera toxin receptor

Figure 14-13. G i ganglioside, a monosialoganglio-side, the receptor in human intestine for cholera toxin.

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). 

A. Bemardi, L. Carrettoni, A. Grosso Ciponte, D. Montib, and S. Sonnino, Second generation mimics of ganglioside GM1 as artificial receptors for Cholera Toxin Replacement of the sialic acid moiety, Bioorg. Med. Chem. Lett., 10 (2000) 2197-2200. 

Figure 7-5 Stereoscopic view of the B5 pentamer of cholera toxin B. The pentamer, known as choleragenoid, has a central hole of 1.5 nm diameter into which a helix from the A subunit is inserted. As viewed here, the front surface of the pentamer has binding sites for the oligosaccharide chains of ganglioside CM, which serves as the toxin receptor. The back side binds the A subunit. See also Box 11-A. From Zhang et al,31...

The metabolism of GSLs has been studied in cultured human fibroblasts from normal subjects, patients with lipid storage diseases, and those with FH. The content of the GSLs, as well as activities of the biosynthetic enzymes, the glycosyltransferases and the lysosomal GSL hydrolases,have been studied. Complex gangliosides, such as M1, GDla, have been found in this cell system to serve as receptors for cholera toxin and thyrotropin, respectively (24-26). More recently, GT1 and GDla have been postulated to be receptors for fibronectin in cultured fibroblasts... 

Gangliosides as Receptors for Cholera Toxin, Tetanus Toxin, and Sendai Virus... 

Subsequent studies in several laboratories have provided further evidence that ganglioside GM1 is the natural biological receptor for cholera toxin ... 

Cuatrecasas, P. Gangliosides and membrane receptors for cholera toxin. Biochemistry, 1973, 12, 3558-3566. 

Holmgren, J. Mansson, J.-E. Svennerholm, L. Tissue receptor for cholera enterotoxin Structural requirements of GM1 ganglioside in toxin binding and inactivation. Medical Biology, 1971, 52, 229-233. 

Spiegel S. Fluorescent derivatives of ganglioside GMl function as receptors for cholera toxin. Biochemistry 1985 24 5947-5952. Gahmberg CG, Andersson LC. Selective radioactive labeling of cell surface sialoglycoproteins by periodate-tritiated borohydride. J. Biol. Chem. 1977 252 5888-5894. 

Pacnszka T, Bradley RM, Fishman PH. Neoglycolipid analogues of ganglioside GMi as functional receptors of cholera toxin. Biochemistry 1991 30 2563-2570. 

Cholera toxin and E. call heat-labile toxin ADP-ribosylate the a-subunit of trimeric G-proteins (Gj) so that they are unable to hydrolyze GTP (Casey and Gilman, 1988 Neer and Claphan, 1988). As a result, the adenylate cyclase stays in a persistently active state. The toxin is taken up from the apical pole of the enterocytes, whereas the adenylate cyclase is located at the basolateral side. Since membrane glycolipids such as the toxin receptor (ganglioside GMi) tend not to cross tight junctions, it is unlikely that the toxin reaches the basolateral side by lateral diffusion. Most likely it enters the cytosol and diffuses to the target which is also located at the cytosolic side of the membrane. 

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