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Toxins 2014, 6(11), 3098-3116; doi:10.3390/toxins6113098

Uptake and Processing of the Cytolethal Distending Toxin by Mammalian Cells

Department of Microbiology, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104, USA
Received: 19 September 2014 / Revised: 10 October 2014 / Accepted: 10 October 2014 / Published: 31 October 2014
(This article belongs to the Special Issue Intracellular Traffic and Transport of Bacterial Protein Toxins)
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Abstract

The cytolethal distending toxin (Cdt) is a heterotrimeric holotoxin produced by a diverse group of Gram-negative pathogenic bacteria. The Cdts expressed by the members of this group comprise a subclass of the AB toxin superfamily. Some AB toxins have hijacked the retrograde transport pathway, carried out by the Golgi apparatus and endoplasmic reticulum (ER), to translocate to cytosolic targets. Those toxins have been used as tools to decipher the roles of the Golgi and ER in intracellular transport and to develop medically useful delivery reagents. In comparison to the other AB toxins, the Cdt exhibits unique properties, such as translocation to the nucleus, that present specific challenges in understanding the precise molecular details of the trafficking pathway in mammalian cells. The purpose of this review is to present current information about the mechanisms of uptake and translocation of the Cdt in relation to standard concepts of endocytosis and retrograde transport. Studies of the Cdt intoxication process to date have led to the discovery of new translocation pathways and components and most likely will continue to reveal unknown features about the mechanisms by which bacterial proteins target the mammalian cell nucleus. Insight gained from these studies has the potential to contribute to the development of novel therapeutic strategies. View Full-Text
Keywords: AB toxin; Aggregatibacter actinomycetemcomitans; cytolethal distending toxin; endocytosis; endoplasmic reticulum; Golgi; nuclear localization signal; retrograde transport AB toxin; Aggregatibacter actinomycetemcomitans; cytolethal distending toxin; endocytosis; endoplasmic reticulum; Golgi; nuclear localization signal; retrograde transport
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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DiRienzo, J.M. Uptake and Processing of the Cytolethal Distending Toxin by Mammalian Cells. Toxins 2014, 6, 3098-3116.

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