Ms. Jacewicz et al., PATHOGENESIS OF SHIGELLA DIARRHEA .17. A MAMMALIAN-CELL MEMBRANE GLYCOLIPID, GB3, IS REQUIRED BUT NOT SUFFICIENT TO CONFER SENSITIVITY TO SHIGA TOXIN, The Journal of infectious diseases, 169(3), 1994, pp. 538-546
Shiga toxin recognizes a galactose-alpha 1 --> 4-galactose terminal gl
ycolipid, globotriaosylceramide (Gb3), in sensitive mammalian cells an
d is translocated by endocytosis to the cytoplasm, where it blocks pro
tein synthesis. To determine if Gb3 is both required and sufficient fo
r toxicity, Gb3 content in cells was altered by blocking key biosynthe
tic or degradative path enzymes with specific inhibitors. The resultin
g decrease or increase in cellular Gb3 was associated with a decrease
or increase in binding of and response to Shiga toxin. Toxin-resistant
Gb3-deficient variants of sensitive cells fused with liposomes contai
ning Gb3 but not globotetraosylceramide (Gb4) became susceptible, wher
eas fusion of Gb3 liposomes to naturally resistant Gb3-deficient CHO c
ells increased toxin binding but not cytotoxicity. These data demonstr
ate that Gb3 is required, but not sufficient, for the action of Shiga
toxin and suggest the existence of a toxin translocation mechanism lin
ked to surface glycolipids that is not expressed in CHO cells.