Interaction of cholera toxin and membrane GM1 ganglioside of small intestine.

Holmgren, Jan; Lönnroth, Ivar; Månsson, Jan‐Eric; Svennerholm, Lars

doi:10.1073/pnas.72.7.2520

Cited by 348 publications

(214 citation statements)

References 26 publications

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“…Despite this close similarity, the two toxins differ significantly in their receptor-binding specificities. Both CT and LT bind with high affinity to ganglioside GM1, Gal␤3GalNac␤4(NeuAc␣3)Gal␤4Glc␤1Cer (Holmgren et al, 1973;1975). In addition, LT also binds significantly to glycoprotein receptors present in the intestines of several species (Griffiths and Critchley, 1991;Holmgren et al, 1982;Shida et al, 1996), to polyglycosylceramides (PGCs), complex glycolipids with carbohydrate chains of more than 30 saccharides (Karlsson et al, 1996), and with low affinity to other glycosphingolipids including GM2, asialo-GM1 and neolactotetraosylceramide (paragloboside) (Fukuta et al, 1988;Teneberg et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Structural basis for differential receptor binding of cholera and Escherichia coli heat‐labile toxins: influence of heterologous amino acid substitutions in the cholera B‐subunit

Bäckström

Shahabi

Johansson

et al. 1997

Molecular Microbiology

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SummaryThe closely related B-subunits of cholera toxin (CTB) and Escherichia coli heat-labile enterotoxin (LTB) both bind strongly to GM1 ganglioside receptors but LTB can also bind to additional glycolipids and glycoproteins. A number of mutant CT B-subunits were generated by substituting CTB amino acids with those at the corresponding positions in LTB. These were used to investigate the influence of specific residues on receptor-binding specificity. A mutated CTB protein containing the first 25 residues of LTB in combination with LTB residues at positions 94 and 95, bound to the same extent as native LTB to both delipidized rabbit intestinal cell membranes, complex glycosphingolipids (polyglycosylceramides) and neolactotetraosylceramide, but not to non-GM1 intestinal glycosphingolipids. In contrast, when LTB amino acid substitutions in the 1-25 region were combined with those in the 75-83 region, a binding as strong as that of LTB to intestinal glycosphingolipids was observed. In addition, a mutant LTB with a single Gly-33→Asp substitution that completely lacked affinity for both GM1 and non-GM1 glycosphingolipids could still bind to receptors in the intestinal cell membranes and to polyglycosylceramides. We conclude that the extra, non-GM1 receptors for LTB consist of both sialylated and non-sialylated glycoconjugates, and that the binding to either class of receptors is influenced by different amino acid residues within the protein.

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Section: Introductionmentioning

confidence: 99%

Structural basis for differential receptor binding of cholera and Escherichia coli heat‐labile toxins: influence of heterologous amino acid substitutions in the cholera B‐subunit

Bäckström

Shahabi

Johansson

et al. 1997

Molecular Microbiology

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“…Il a été observé que la toxine LT démontre un attachement 10 fois plus fort que la toxine CT dans le petit intestin de lapin. Un site récepteur membranaire additionnel à GM1 pour LT a désormais été identifié [4,55,65,116,134,166]. Il est surprenant que deux espèces bactériennes qui colonisent le même tissu, l'intestin grêle, et utilisent les mêmes récepteur et cible d'action pour leurs toxines, diffèrent dans l'adhérence initiale de la bactérie au tissu.…”

Section: Sites D'attachement Multifactorielsunclassified

“…coli reconnaît égale-ment le récepteur membranaire GM1, par l'intermédiaire de ses sous-unités B, et conduit aux mêmes effets dans les cellules et dans l'intestin que la toxine CT [56,65,133,136]. Alors que la toxine CT s'attache au GM1 avec une grande sélectivité, la toxine LT fixe d'autres récepteurs membranaires, non reconnus par CT, et qui sont fonctionnels pour LT [55,67,116,134,166].…”

Section: Activation De L'adénylate Cyclaseunclassified

Les récepteurs des entérotoxines bactériennes

Rousset

2000

Vet. Res.

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-Bacterial enterotoxin receptors. Enteric bacterial toxins display a great diversity in their structure, molecular weight and mechanism of action. The interaction of enterotoxins with the intestinal mucosa either leads to a direct effect on the cell membrane or an effect on signal transduction within eukaryotic cells. However, before a toxin can affect a cell, it must after its secretion by a microorganism, recognise and bind to a specific surface molecule, its receptor. Membrane receptors of bacterial enterotoxins have been identified as protein, glycoprotein or glycolipid in nature. The chemical nature of the molecules acting as receptors is crucial and during evolution they have been carefully selected. Some toxins, after their interaction with a receptor molecule, will transduce a signal across the cell membrane while remaining at the cell surface. Other toxins, after this initial binding step with a receptor, will be internalised. Others can form pores leading to leakage of cellular components and cell lysis. Receptors that have been identified often comprise a saccharidic chain that is directly involved in the recognition and binding of the toxin. Today, models explaining toxin-receptor interactions are more complex, including multistep events. This review summarises the knowledge of the interactions between bacterial toxins and membrane receptors present on intestinal mucosa. receptor / intestine / enterotoxin / binding epitope / glycosphingolipidRésumé -Les toxines bactériennes entériques présentent une grande diversité autant dans leur structure que dans leur poids moléculaire et leur mécanisme d'action. L'interaction des entérotoxines avec la muqueuse intestinale conduit soit à un effet direct sur la paroi cellulaire de la cellule hôte, soit à un dérèglement des voies de signalisation de celle-ci. Toutefois, avant même d'affecter la cellule cible, la toxine sécrétée par le micro-organisme devra reconnaître et s'attacher à une molécule présente à la surface cellulaire, son récepteur. Les récepteurs membranaires des entérotoxines bactériennes peuvent être de nature protéique, glycoprotéique ou glycolipidique. La nature chimique de ces récepteurs, sur laquelle repose la spécificité, est primordiale et au cours de l'évolution ceuxci ont été soigneusement sélectionnés. Certaines toxines, une fois en contact avec leur récepteur, envoient un signal à l'intérieur de la cellule tout en demeurant à la surface alors que d'autres toxines sont internalisées. Enfin, certaines toxines bactériennes peuvent former des pores dans la membrane Vet. Res. 31 (2000)

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“…Exogenous gangliosides are known to insert in the plasma membrane of cells (Holmgren et al, 1975;Markwell et al, 1981;Superti et al, 1986a, b). Our working hypothesis was based on the recovery of susceptibility to rotavirus infection by the insertion of gangliosides into the plasma membranes of neuraminidase-pretreated cells.…”

Section: Restoration Of Susceptibility To Infection By Gangliosides Amentioning

confidence: 99%

Gangliosides as binding sites in SA-11 rotavirus infection of LLC-MK2 cells

Superti

Donelli

1991

Journal of General Virology

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The chemical nature of receptors involved in the attachment of simian rotavirus (SA-11) to a monkey kidney cell line (LLC-MK2) was investigated. Enzymic treatment of cells before virus infection indicated that membrane proteins and phospholipids are not involved in virus attachment, whereas sialic acid and galactose participate in the receptor structure to differing extents. Incubation ofSA-11 with bovine brain gangliosides before infection strongly reduced its ability to bind to cell membranes. Similar experiments with individual purified gangliosides from bovine brain showed that virus infection was prevented by preincubation with GM1. Moreover, desialylated cells regained susceptibility to virus infection when coated with whole gangliosides or GM1 immediately after Clostridium perfringens neuraminidase treatment. The binding of SA-11 to whole gangliosides or GM1 was quantified by an ELISA procedure. The results suggest that gangliosides, mainly GM 1, are part of the receptor structure for SA-I 1 of susceptible LLC-MK2 cells.

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Interaction of cholera toxin and membrane GM1 ganglioside of small intestine.

Abstract: Ganglioside GM, was isolated from the small intestinal mucosa of man, pig, and beef and amounted to 0.1, 2.0, and 43 nmol per g fresh weight, respectively.

Cited by 348 publications

References 26 publications

Structural basis for differential receptor binding of cholera and Escherichia coli heat‐labile toxins: influence of heterologous amino acid substitutions in the cholera B‐subunit

Structural basis for differential receptor binding of cholera and Escherichia coli heat‐labile toxins: influence of heterologous amino acid substitutions in the cholera B‐subunit

Les récepteurs des entérotoxines bactériennes

Gangliosides as binding sites in SA-11 rotavirus infection of LLC-MK2 cells

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