Document Detail

Secreted Autotransporteur Toxin (Sat) Triggers Autophagy in Epithelial Cells that Relies on Cell-Detachment.
MedLine Citation:
PMID:  21501364     Owner:  NLM     Status:  Publisher    
The Secreted autotransporter toxin, Sat, which belongs to the subfamily of serine protease autotransporters of Enterobacteriaceae (SPATEs), acts as a virulence factor in extraintestinal and intestinal pathogenic strains of Escherichia coli. We observed that HeLa cells exposed to the cell-free culture supernatant of recombinant strain AAEC185(Sat) containing the Sat toxin (CFCS(Sat) ), displayed dramatic disorganization of the F-actin cytoskeleton before loosening cell-to-cell junctions and detachment. Examination of the effect of Sat on GFP-microtubule-associated protein light chain 3 (LC3) HeLa cells revealed that CFCS(Sat) -induced autophagy follows CFCS(Sat) -induced F-actin cytoskeleton rearrangement. The induced autophagy shows an acceleration of the autophagy flux soon after Sat treatment, followed later by a blockade of the flux leading to the accumulation of large GFP-LC3-positive vacuoles in the cell cytoplasm. CFCS(Sat) did not induce cell-detachment in autophagy-deficient mouse embryonic fibroblasts (MEF) in contrast with wild-type MEF. The CFCS(Sat) -induced large GFP-LC3 dots do not display the characteristics of autophagolysosomes including expression of cathepsin D and Lamp-1 and 2 proteins, and Lysotracker Red- and DQ-BSA-positive labeling. We provide evidences that CFCS(Sat) -induced autophagy is not a cell response intended to get rid of the intracellular toxin. By a pharmacological blockers approach, we found that the blockade of Erk1/2 and p38 MAPKs, but not JNK, inhibited the CFCS(Sat) -induced autophagy and cell detachment whereas phosphatidylinositol-3 kinase blockers inhibiting canonical autophagy were inactive. When attached CFCS(Sat) -treated cells start to detach they showed caspase-independent cell death and rearrangements of the focal adhesion-associated vinculin and paxillin. Collectively, our results support that Sat triggers autophagy in epithelial cells that relies on its cell-detachment effect.
Vanessa Liévin-Le Moal; Yannick Comenge; Vincent Ruby; Raymonde Amsellem; Valérie Nicolas; Alain L Servin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-21
Journal Detail:
Title:  Cellular microbiology     Volume:  -     ISSN:  1462-5822     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-4-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 Blackwell Publishing Ltd.
INSERM, UMR 756 « Signalisation and Physiopathology of Epithelial cells», Châtenay-Malabry, France IFR 141 Plateforme Imagerie cellulaire, Faculté de Pharmacie, Châtenay-Malabry, France. Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.
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