Vibrio choleraehemagglutinin/protease (HA/protease) causes morphological changes in cultured epithelial cells and perturbs their paracellular barrier function

1996 ◽  
Vol 21 (2) ◽  
pp. 111-123 ◽  
Author(s):  
Zhengyang Wu ◽  
Debra Milton ◽  
Pia Nybom ◽  
Anita Sjö ◽  
Karl-Eric Magnusson
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Morphological Changes ◽  
Cultured Epithelial Cells

scholarly journals Identification of a Novel Virulence Factor in Clostridium Difficile That Modulates Toxin Sensitivity of Cultured Epithelial Cells

2011 ◽  
Vol 79 (9) ◽  
pp. 3810-3820 ◽  
Author(s):  
Masashi Miura ◽  
Haru Kato ◽  
Osamu Matsushita
Keyword(s):  
Clostridium Difficile ◽  
Epithelial Cells ◽  
Culture Filtrate ◽  
Morphological Changes ◽  
Hypothetical Protein ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Cultured Epithelial Cells ◽  
Toxin Sensitivity ◽  
In Cells

ABSTRACTTwo glucosylating toxins named toxins A and B play a role in the pathogenesis ofClostridium Difficileinfection. The interaction of the toxins with host cell factors proceeds to downstream stages of cytotoxic effects in cells, in which involvement of otherC. difficilefactors remains unknown. We utilized culture filtrate ofC. difficilewith a low dilution to characterize the influence of putative minor proteins on the organization of the actin cytoskeleton in cultured epithelial cells and found a previously uncharacterized F-actin aggregated structure, termed “actin aggregate,” at the juxtanuclear region. We reasoned that formation of actin aggregate was due to an additional factor(s) in the culture filtrate rather than the glucosylating toxins, because treatment of purified toxins rarely caused actin aggregate in cells. We focused on a previously uncharacterized hypothetical protein harboring a KDEL-like sequence as a candidate. The product of the candidate gene was detected in culture filtrate ofC. difficileATCC 9689 and was renamed Srl. Purified glutathioneS-transferase-tagged Srl triggered formation of actin aggregate in the cells in the presence of either toxin A or B and enhanced cytotoxicity of each of the two toxins, including decreases in both cell viability and transepithelial resistance of cultured epithelial monolayer, although the recombinant Srl alone did not show detectable cytotoxicity. Srl-neutralized culture filtrate partially inhibited morphological changes of the cells in parallel with decreased actin aggregate formation in the cells. Thus, Srl might contribute to the modulation of toxin sensitivity of intestinal epithelial cells by enhancing cytotoxicity ofC. difficiletoxins.

Vimentin organizing centre in cultured epithelial cells

Pathology ◽  
1984 ◽  
Vol 16 (4) ◽  
pp. 393-395 ◽  
Author(s):  
John S. Pedersen ◽  
J.R. Underwood ◽  
B.H. Toh
Keyword(s):  
Epithelial Cells ◽  
Cultured Epithelial Cells

scholarly journals Cbl-transforming Variants Trigger a Cascade of Molecular Alterations That Lead to Epithelial Mesenchymal Conversion

2000 ◽  
Vol 11 (10) ◽  
pp. 3397-3410 ◽  
Author(s):  
Tanya M. Fournier ◽  
Louie Lamorte ◽  
Christiane R. Maroun ◽  
Mark Lupher ◽  
Hamid Band ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Morphological Changes ◽  
Cell Spreading ◽  
Mesenchymal Transition ◽  
Amino Terminal ◽  
Src Homology ◽  
Hepatocyte Growth

Dispersal of epithelial cells is an important aspect of tumorigenesis, and invasion. Factors such as hepatocyte growth factor induce the breakdown of cell junctions and promote cell spreading and the dispersal of colonies of epithelial cells, providing a model system to investigate the biochemical signals that regulate these events. Multiple signaling proteins are phosphorylated in epithelial cells during hepatocyte growth factor–induced cell dispersal, including c-Cbl, a protooncogene docking protein with ubiquitin ligase activity. We have examined the role of c-Cbl and a transforming variant (70z-Cbl) in epithelial cell dispersal. We show that the expression of 70z-Cbl in Madin-Darby canine kidney epithelial cells resulted in the breakdown of cell–cell contacts and alterations in cell morphology characteristic of epithelial–mesenchymal transition. Structure–function studies revealed that the amino-terminal portion of c-Cbl, which corresponds to the Cbl phosphotyrosine-binding/Src homology domain 2 , is sufficient to promote the morphological changes in cell shape. Moreover, a point mutation at Gly-306 abrogates the ability of the Cbl Src homology domain 2 to induce these morphological changes. Our results identify a role for Cbl in the regulation of epithelial–mesenchymal transition, including loss of adherens junctions, cell spreading, and the initiation of cell dispersal.

scholarly journals JunD Represses Transcription and Translation of the Tight Junction Protein Zona Occludens-1 Modulating Intestinal Epithelial Barrier Function

2008 ◽  
Vol 19 (9) ◽  
pp. 3701-3712 ◽  
Author(s):  
Jie Chen ◽  
Lan Xiao ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Lan Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Mrna Translation ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function

The AP-1 transcription factor JunD is highly expressed in intestinal epithelial cells, but its exact role in maintaining the integrity of intestinal epithelial barrier remains unknown. The tight junction (TJ) protein zonula occludens (ZO)-1 links the intracellular domain of TJ-transmembrane proteins occludin, claudins, and junctional adhesion molecules to many cytoplasmic proteins and the actin cytoskeleton and is crucial for assembly of the TJ complex. Here, we show that JunD negatively regulates expression of ZO-1 and is implicated in the regulation of intestinal epithelial barrier function. Increased JunD levels by ectopic overexpression of the junD gene or by depleting cellular polyamines repressed ZO-1 expression and increased epithelial paracellular permeability. JunD regulated ZO-1 expression at the levels of transcription and translation. Transcriptional repression of ZO-1 by JunD was mediated through cAMP response element-binding protein-binding site within its proximal region of the ZO-1-promoter, whereas induced JunD inhibited ZO-1 mRNA translation by enhancing the interaction of the ZO-1 3′-untranslated region with RNA-binding protein T cell-restricted intracellular antigen 1-related protein. These results indicate that JunD is a biological suppressor of ZO-1 expression in intestinal epithelial cells and plays a critical role in maintaining epithelial barrier function.

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