Internalized pseudomonas exotoxin A can exploit multiple pathways to reach the endoplasmic reticulum
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. ISSN 1398-9219Full text not available from this repository.
Official URL: http://dx.doi.org/10.1111/j.1600-0854.2006.00391.x
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|
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Divisions:||Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)|
|Journal or Publication Title:||Traffic|
|Publisher:||Wiley-Blackwell Publishing Ltd.|
|Official Date:||23 December 2005|
|Number of Pages:||15|
|Page Range:||pp. 379-393|
|Access rights to Published version:||Restricted or Subscription Access|
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