Open AccessCholera Toxin and Cell Growth: Role of Membrane Gangliosides
Author(s) -
Morley D. Hollenberg,
Peter H. Fishman,
Vann Bennett,
Pedro Cuatrecasas
Publication year - 1974
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.71.10.4224
Subject(s) - cholera toxin , ganglioside , toxin , cyclase , biology , adenylate kinase , pertussis toxin , biochemistry , cell culture , receptor , microbiology and biotechnology , g protein , genetics
The binding of cholera toxin to three transformed mouse cell lines derived from the same parent strain, and the effects of the toxin on DNA synthesis and adenylate cyclase activity, vary in parallel with the ganglioside composition of the cells. TAL/N cells of early passage, which contain large quantities of gangliosides GM3 , GM2 , GM1 , and GDla , as well as the glycosyltransferases necessary for the synthesis of these gangliosides, bind the most cholera toxin and are the most sensitive to its action. TAL/N cells of later passage, which lack chemically detectable GM1 and GDla and which have no UDP-Gal:GM2 galactosyltransferase activity, are intermediate in binding and response to the toxin. SVS AL/N cells, which lack GM2 in addition to GM1 and GDla and which have little detectable UDP-GalNAc:GM3 N -acetylgalactosaminyltransferase activity, bind the least amount of toxin. The SVS AL/N cells are the least responsive to inhibition of DNA synthesis and stimulation of adenylate cyclase activity by cholera toxin. Gangliosides (especially GM1 ), which appear to be the natural membrane receptors for cholera toxin, may normally have important roles in the regulation of cell growth and cAMP-mediated responses.