To investigate the role of the KDEL receptor in the retrieval of protein toxins 
to the mammalian cell endoplasmic reticulum (ER), lysozyme variants containing 
AARL or KDEL C-terminal tags, or the human KDEL receptor, have been expressed in 
toxin-treated COS 7 and HeLa cells. Expression of the lysozyme variants and the 
KDEL receptor was confirmed by immunofluorescence. When such cells were 
challenged with diphtheria toxin (DT) or Escherichia coli Shiga-like toxin 1 
(SLT-1), there was no observable difference in their sensitivities as compared 
to cells which did not express these exogenous proteins. By contrast, the 
cytotoxicity of Pseudomonas exotoxin A (PE) is reduced by expressing 
lysozyme-KDEL, which causes a redistribution of the KDEL receptor from the Golgi 
complex to the ER, and cells are sensitised to this toxin when they express 
additional KDEL receptors. These data suggest that, in contrast to SLT-1, PE can 
exploit the KDEL receptor in order to reach the ER lumen where it is believed 
that membrane transfer to the cytosol occurs. This contention was confirmed by 
microinjecting into Vero cells antibodies raised against the cytoplasmically 
exposed tail of the KDEL receptor. Immunofluorescence confirmed that these 
antibodies prevented the retrograde transport of the KDEL receptor from the 
Golgi complex to the ER, and this in turn reduced the cytotoxicity of PE, but 
not that of SLT-1, to these cells.