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How Ricin and Shiga Toxin Reach the Cytosol of Target Cells: Retrotranslocation from the Endoplasmic Reticulum

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Ricin and Shiga Toxins

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 357))

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.

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Abbreviations

CTx:

Cholera toxin

CTxA1:

CTx A1 toxic chain

CTxB:

CTx B chain

ER:

Endoplasmic reticulum

ERAD:

ER associated protein degradation

Gb3:

Glycolipid globotriaosylceramide, the STx receptor.

PDI:

Protein disulphide isomerise

RTA:

Ricin A chain

RTB:

Ricin B chain

STx:

Shiga toxin

STxA1:

STx A1 toxic chain

STxB:

STx B chain

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Acknowledgments

This work was supported by Wellcome Trust Programme Grant 080566/Z/06/Z and National Institutes of Health Grant 5U01AI65869-02.

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  1. School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK

    Robert A. Spooner & J. Michael Lord

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  1. Robert A. Spooner
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  2. J. Michael Lord
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Correspondence to J. Michael Lord .

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  1. , Division of Infectious Diseases, NYDOH, Wadsworth Center, New Scotland Ave 120, Albany, 12208, New York, USA

    Nicholas Mantis

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Spooner, R.A., Lord, J.M. (2011). How Ricin and Shiga Toxin Reach the Cytosol of Target Cells: Retrotranslocation from the Endoplasmic Reticulum. In: Mantis, N. (eds) Ricin and Shiga Toxins. Current Topics in Microbiology and Immunology, vol 357. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2011_154

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