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Entry of Protein Toxins into Mammalian Cells by Crossing the Endoplasmic Reticulum Membrane: Co-opting Basic Mechanisms of Endoplasmic Reticulum-Associated Degradation

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Dislocation and Degradation of Proteins from the Endoplasmic Reticulum

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 300))

Abstract

The catalytic polypeptides of certain bacterial and plant protein toxins reach their substrates in the cytosol of mammalian cells by retro-translocation from the endoplasmic reticulum (ER). Emerging evidence indicates that these proteins subvert the ER-associated protein degradation (ERAD) pathway that normally removes misfolded or unassembled proteins from the ER, to achieve retrotranslocation. Upon entering the ER lumen, the toxins are unfolded to be perceived as ERAD substrates. Toxins that retro-translocate from the ER have an unusually low lysine content to avoid ubiquitin-mediated proteasomal degradation. This allows the exported toxins to refold into the proteasome-resistant, biologically active conformation, and leads to cellular intoxication.

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Authors and Affiliations

  1. Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, UK

    J. M. Lord & L. M. Roberts

  2. The Division of Gastroenterology, Childrens Hospital Boston and the Harvard Digestive Diseases Center and the Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA

    W. I. Lencer

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  1. J. M. Lord
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  2. L. M. Roberts
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  3. W. I. Lencer
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Editors and Affiliations

  1. Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands

    Emmanuel Wiertz Ph. D.  & Marjolein Kikkert Ph. D.  & 

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Lord, J.M., Roberts, L.M., Lencer, W.I. (2006). Entry of Protein Toxins into Mammalian Cells by Crossing the Endoplasmic Reticulum Membrane: Co-opting Basic Mechanisms of Endoplasmic Reticulum-Associated Degradation. In: Wiertz, E., Kikkert, M. (eds) Dislocation and Degradation of Proteins from the Endoplasmic Reticulum. Current Topics in Microbiology and Immunology, vol 300. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-28007-3_7

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