Document Detail


Clathrin-dependent trafficking of subtilase cytotoxin, a novel AB5 toxin that targets the endoplasmic reticulum chaperone BiP.
MedLine Citation:
PMID:  18042253     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Subtilase cytotoxin (SubAB) is the prototype of a new family of AB5 cytotoxins produced by Shiga toxigenic Escherichia coli. Its cytotoxic activity is due to its capacity to enter cells and specifically cleave the endoplasmic reticulum (ER) chaperone BiP. However, its trafficking within target cells has not been investigated previously. In Vero cells, fluorescence colocalization with subcellular markers established that SubAB is trafficked from the cell surface to the ER via a retrograde pathway similar, but not identical, to those of Shiga toxin (Stx) and cholera toxin (Ctx), with their pathways converging at the Golgi. The clathrin inhibitor phenylarsine oxide prevented SubAB entry and BiP cleavage in SubAB-treated Vero, HeLa and N2A cells, while cholesterol depletion did not, demonstrating that, unlike either Stx or Ctx, SubAB internalization is exclusively clathrin-dependent.
Authors:
Damien C Chong; James C Paton; Cheleste M Thorpe; Adrienne W Paton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-11-27
Journal Detail:
Title:  Cellular microbiology     Volume:  10     ISSN:  1462-5822     ISO Abbreviation:  Cell. Microbiol.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-08     Completed Date:  2008-03-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  795-806     Citation Subset:  IM    
Affiliation:
School of Molecular and Biomedical Science, University of Adelaide, SA 5005, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arsenicals / pharmacology
Cercopithecus aethiops
Clathrin / antagonists & inhibitors,  metabolism*
Endoplasmic Reticulum / chemistry,  enzymology*
Enzyme Inhibitors / pharmacology
Escherichia coli Proteins / metabolism*
Golgi Apparatus / chemistry
Heat-Shock Proteins / antagonists & inhibitors*
Hela Cells
Humans
Microscopy, Fluorescence
Molecular Chaperones / antagonists & inhibitors*
Shiga-Toxigenic Escherichia coli / physiology*
Subtilisins / metabolism*
Vero Cells
Grant Support
ID/Acronym/Agency:
P30DK-34928/DK/NIDDK NIH HHS; R01AI-068715/AI/NIAID NIH HHS; R01AI-59509/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Arsenicals; 0/Clathrin; 0/Enzyme Inhibitors; 0/Escherichia coli Proteins; 0/Heat-Shock Proteins; 0/Molecular Chaperones; 0/molecular chaperone GRP78; 637-03-6/oxophenylarsine; EC 3.4.21.-/Subtilisins; EC 3.4.21.-/subtilase cytotoxin, E coli

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