UNSPECIFIED. (2006) Internalized pseudomonas exotoxin A can exploit multiple pathways to reach the endoplasmic reticulum. TRAFFIC, 7 (4). pp. 379-393. ISSN 1398-9219

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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
Subjects:	Q Science > QH Natural history > QH301 Biology
Journal or Publication Title:	TRAFFIC
Publisher:	BLACKWELL PUBLISHING
ISSN:	1398-9219
Date:	April 2006
Volume:	7
Number:	4
Number of Pages:	15
Page Range:	pp. 379-393
Identification Number:	10.1111/j.1600-0854.2006.00391.x\
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/33781

Data sourced from Thomson Reuters' Web of Knowledge

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