title: How ricin and Shiga toxin reach the cytosol of target cells: retrotranslocation from the endoplasmic reticulum.
abstract: 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.
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK. R.A.Spooner@warwick.ac.uk
authors.forename: Robert A
authors.initials: RA
authors.lastname: Spooner
authors.forename: J Michael
authors.initials: JM
authors.lastname: Lord
mesh_terms: D003600:Cytosol / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D021381:Protein Transport; D012276:Ricin / Q000737:chemistry / Q000378:metabolism*; D022621:Shiga Toxin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D022621:Shiga Toxin; D012276:Ricin