Addition of an ER retention signal to the ricin A chain increases the cytotoxicity of the holotoxin.
With the exception of diphtheria toxin, which translocates from acidified endosomes, the intracellular organelle from which the catalytic moieties of several plant and bacterial toxins enter the target cell during endocytic uptake has not been identified. We have recently proposed that some toxins may travel the entire secretory pathway in reverse, moving from the cell surface to the lumen of the ER, before entering the cytosol. Several bacterial toxins have the ER retention sequence KDEL or a related analogue at their carboxyl termini, suggesting that the KDEL receptor may play a role in delivering these toxins to the ER. Here we provide further support for this possibility since the cytotoxicity of ricin, which lacks a KDEL sequence, can be significantly increased by adding KDEL to the C-terminus of its A chain.
Wales
R
R
Department of Biological Sciences, University of Warwick, Coventry, United Kingdom.
Chaddock
J A
JA
Roberts
L M
LM
Lord
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism / Q000633:toxicity; D015183:Restriction Mapping; D012276:Ricin / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D014709:Vero Cells
D011994:Recombinant Proteins; D012276:Ricin