Cholera Toxin and Cell Growth: Role of Membrane Gangliosides

Hollenberg, Morley D.; Fishman, Peter H.; Bennett, Vann; Cuatrecasas, Pedro

doi:10.1073/pnas.71.10.4224

Cited by 87 publications

(50 citation statements)

References 52 publications

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“…raminidase-sensitive gangliosides (i.e., GDia and GTI) on the cell surface are being converted to GM1, which is neuraminidase resistant, and new toxin-binding sites are being generated. Similar increases in cholera toxin binding after the treatment of other cultured cell lines with neuraminidase have been observed (23,25). DISCUSSION Evidence is presented here that gangliosides inhibit cell adhesion by binding to fibronectin.…”

Section: Resultssupporting

confidence: 63%

Ganglioside inhibition of fibronectin-mediated cell adhesion to collagen.

Kleinman¹,

Martin²,

Fishman³

1979

Proc. Natl. Acad. Sci. U.S.A.

239

107

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Fibronectin mediates the adhesion of cells to col1agen by first binding to the collagen substrate, followed by attachment of the cells to the fibronectin-collagen complex. Bovine brain gangliosides were found to block fibronectinmediated cell adhesion to collagen in a concentration-dependent manner. The gangliosides did not block the binding of fibronectin to collagen but did prevent the attachment of the cells to the fibronectin-collagen complex. Of the individual gangliosides tested, GT1 and GDia were the most effective inhibitors followed by GD1b >> GM1 >> GM2; GM3 was not an inhibitor. The inhibition of cell adhesion also was observed with the oligosaccharide portion of the gangliosides, but not with ceramides or with a variety of free sugars or glycosaminoglycans. Mild periodate oxidation of mixed gangliosides or of GDia modified their sialic acid residues and the oxidized gangliosides were no longer inhibitory; subsequent reduction with NaBH4 did not restore the inhibitory activity of the modified gangliosides. These results suggest that specific gangliosides or related sialic acid-containing glycoconjugates on the cell surface may act as the receptors for fibronectin. Most cells require an appropriate substratum for growth in culture. A variety of cells use fibronectin, a large extrinsic matrix protein to adhere either to plastic (1) or to collagen substrates (2). An identical or very similar protein, cold insoluble globulin, is present in serum, and the serum form of fibronectin promotes the attachment of freshly trypsinized cells. Fibronectin prepared from either cells or serum is equally active in promoting cell attachment (3). With collagen substrates, fibronectin binds to the collagen substratum first (2, 4). Then the cells, in the presence of Ca2+ or Mg2+ in an energy-dependent process (5), adhere to the fibronectin-collagen complex. Fibronectin binds to all mammalian collagens that have been tested so far and it also binds to fibrin (6). In the al(I) chain of collagen, it binds to a specific amino acid sequence lacking carbohydrate (7)(8)(9)(10). These interactions are not cation dependent and can be broken by 1 M KBr (11) or 6 M urea (12). Fibrinogen (13) and collagen affinity columns (11, 12) have proved useful in the purification of fibronectin from serum and from conditioned culture medium.Little is known about the interaction of fibronectin with the cell surface or the nature of the membrane component(s) to which fibronectin binds. One approach to their identification is to test various cell surface components for their ability to interact with the fibronectin-collagen complex and thereby prevent cell attachment. Gangliosides are well-defined membrane components, and a specific ganglioside, GM,, functions as the membrane receptor for cholera toxin (14). This role for GM, was elucidated from the original observation that gangliosides block the biological effects of the toxin (15). We now report that certain gangliosides block cell adhesion promoted by the fibronectin in serum.MATERIALS ...

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Section: Resultssupporting

confidence: 63%

Ganglioside inhibition of fibronectin-mediated cell adhesion to collagen.

Kleinman¹,

Martin²,

Fishman³

1979

Proc. Natl. Acad. Sci. U.S.A.

239

107

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“…Greaves (1975) reported by using the binding method of cholera toxin, acuteleukaemia cells had no GM1 gangliosides. GM1 ganglioside is considered to play an important role in the regulation of cell growth and cyclic AMP-mediated responses (Hollenberg et al, 1974). In this study, however, Band 5 ganglioside with similar Rf value to GM1 ganglioside was detectable in certain leukaemic blasts.…”

Section: Methodscontrasting

confidence: 54%

Characterization of gangliosides in human leucocytes

Tsuboyama¹,

Takaku²,

Sakamoto³

et al. 1980

Br J Cancer

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Summary.-Lipids extracted from leucocyte pellets with chloroform-methanol were applied to a DEAE-Sephadex column and the gangliosides were eluted with 02M sodium acetate in methanol. The eluate was desalted by Sephadex G-50 column chromatography. The purified ganglioside was spotted on the high-performance thin-layer plate. The plate was developed and sprayed with resorcinol reagents and heated.Seventeen bands of gangliosides were demonstrated in normal human leucocytes. The composition of these gangliosides was different in the various kinds of leucocytes. Amounts of GM3 ganglioside were apparently greater in normal lymphocytes and leukaemic cells than in granulocytes. Among the acute-leukaemic cells, some kinds of complex gangliosides were much more abundant in myelogenous cells than in lymphocytic cells. These changes in ganglioside composition are suggested as new biochemical markers for leukaemic cells.

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“…For bioassay of LATS, the guinea pig or mouse has been used. Cholera enterotoxin also stimulates adenyl cyclase in various endocrine glands (Hollenberg et al, 1974;Gill 1975;Gangully and Guenaugh 1975). For example, cholera enterotoxin stimulates adenyl cyclase activity in thyroid plasma membranes (PM) in a manner similar to TSH or LATS (Mullin et al,l 976 a and b).…”

mentioning

confidence: 99%

Effect of LATS, TSH and cholera toxin on the thyroid gland in nude mice.

et al. 1977

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SynopsisThree thyroid stimulators; LATS, TSH, and cholera toxin, have been tested by bioassay using congenitally athymic homozygous mice (nu/nu), nude mice and control littermates (nu/+) possessing normal thymic function. nu/+ Animals showed a response to LATS similarly to normal white mice of the ddN strain. The assay response to LATS in nu/nu animals was about half that in normal mice. TSH also showed a less stimulating action in nude mice.Cholera toxin made a long acting response similarly to LATS. The response to cholera toxin in nude mice was about half that of normal control mice.The thyroid of nude mice has a receptor for LATS-immunoglobulin, TSH or cholera toxin, which is similar to that of normal mice.

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Cholera Toxin and Cell Growth: Role of Membrane Gangliosides

Cited by 87 publications

References 52 publications

Ganglioside inhibition of fibronectin-mediated cell adhesion to collagen.

Ganglioside inhibition of fibronectin-mediated cell adhesion to collagen.

Characterization of gangliosides in human leucocytes

Effect of LATS, TSH and cholera toxin on the thyroid gland in nude mice.

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