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Internalized pseudomonas exotoxin A can exploit multiple pathways to reach the endoplasmic reticulum
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Smith, Daniel C., Spooner, Robert A. , Watson, P. D., Murray, J. L. , Hodge, T. W., Amessou, Mohamed, Johannes, Ludger, Lord, J.M. and Roberts, L. M. (Lynne M.) (2005) Internalized pseudomonas exotoxin A can exploit multiple pathways to reach the endoplasmic reticulum. Traffic, Volume 7 (Number 4). pp. 379-393. doi:10.4132/KoreanJPathol.2009.43.5.471 ISSN 1398-9219.
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Official URL: http://dx.doi.org/10.1111/j.1600-0854.2006.00391.x
Abstract
Receptor-mediated internalization to the endoplasmic reticulum (ER) and subsequent retro-translocation to the cytosol are essential sequential processes required for the intoxication of mammalian cells by Pseudomonas exotoxin A (PEx). The toxin binds the alpha 2-macroglobulin receptor/low-density lipoprotein receptor-related protein. Here, we show that in HeLa cells, PEx recruits a proportion of this receptor to detergent-resistant microdomains (DRMs). Uptake of receptor-bound PEx involves transport steps both directly from early endosomes to the trans-Golgi network (TGN) independently of Rab9 function and from late endosomes to the TGN in a Rab9-dependent manner. Furthermore, treatments that simultaneously perturb both Arf1-dependent and Rab6-dependent retrograde pathways show that PEx can use multiple routes to reach the ER. The Rab6-dependent route has only been described previously for cargo with lipid-sorting signals. These findings suggest that partial localization of PEx within DRM permits a choice of trafficking routes consistent with a model that DRM-associated toxins reach the ER on a lipid-dependent sorting pathway whilst non-DRM-associated PEx exploits the previously characterized KDEL receptor-mediated uptake pathway. Thus, unexpectedly, an ER-directed toxin with a proteinaceous receptor shows promiscuity in its intracellular trafficking pathways, exploiting routes controlled by both lipid- and protein-sorting signals.
Item Type: | Journal Article | ||||||
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Subjects: | Q Science > QH Natural history > QH301 Biology | ||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010) | ||||||
Journal or Publication Title: | Traffic | ||||||
Publisher: | Wiley-Blackwell Publishing Ltd. | ||||||
ISSN: | 1398-9219 | ||||||
Official Date: | 23 December 2005 | ||||||
Dates: |
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Volume: | Volume 7 | ||||||
Number: | Number 4 | ||||||
Number of Pages: | 15 | ||||||
Page Range: | pp. 379-393 | ||||||
DOI: | 10.4132/KoreanJPathol.2009.43.5.471 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Restricted or Subscription Access |
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