How ricin and Shiga toxin reach the cytosol of target cells: retrotranslocation from the endoplasmic reticulum

Curr Top Microbiol Immunol. 2012;357:19-40. doi: 10.1007/82_2011_154.


A number of protein toxins bind at the surface of mammalian cells and after endocytosis traffic to the endoplasmic reticulum, where the toxic A chains are liberated from the holotoxin. The free A chains are then dislocated, or retrotranslocated, across the ER membrane into the cytosol. Here, in contrast to ER substrates destined for proteasomal destruction, they undergo folding to a catalytic conformation and subsequently inactivate their cytosolic targets. These toxins therefore provide toxic probes for testing the molecular requirements for retrograde trafficking, the ER processes that prepare the toxic A chains for transmembrane transport, the dislocation step itself and for the post-dislocation folding that results in catalytic activity. We describe here the dislocation of ricin A chain and Shiga toxin A chain, but also consider cholera toxin which bears a superficial structural resemblance to Shiga toxin. Recent studies not only describe how these proteins breach the ER membrane, but also reveal aspects of a fundamental cell biological process, that of ER-cytosol dislocation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cytosol / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Intracellular Membranes / metabolism
  • Protein Transport
  • Ricin / chemistry
  • Ricin / metabolism*
  • Shiga Toxin / chemistry
  • Shiga Toxin / metabolism*


  • Shiga Toxin
  • Ricin