Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. (original) (raw)

Research Article Free access | 10.1172/JCI118114

C Fiorentini, G Donelli, S Uzzau, J B Kaper, K Margaretten, X Ding, S Guandalini, L Comstock, and S E Goldblum

Division of Pediatric Gastroenterology and Nutrition, University of Maryland School of Medicine, Baltimore 21201, USA.

Find articles by Fasano, A. in:JCI |PubMed |Google Scholar

Division of Pediatric Gastroenterology and Nutrition, University of Maryland School of Medicine, Baltimore 21201, USA.

Find articles by Fiorentini, C. in:JCI |PubMed |Google Scholar

Division of Pediatric Gastroenterology and Nutrition, University of Maryland School of Medicine, Baltimore 21201, USA.

Find articles by Donelli, G. in:JCI |PubMed |Google Scholar

Division of Pediatric Gastroenterology and Nutrition, University of Maryland School of Medicine, Baltimore 21201, USA.

Find articles by Uzzau, S. in:JCI |PubMed |Google Scholar

Division of Pediatric Gastroenterology and Nutrition, University of Maryland School of Medicine, Baltimore 21201, USA.

Find articles by Kaper, J. in:[JCI](/search/results?q=author.first%5Fname%3A%22J B%22+author.last%5Fname%3A%22Kaper%22&search%5Ftype=advanced) |PubMed |Google Scholar

Division of Pediatric Gastroenterology and Nutrition, University of Maryland School of Medicine, Baltimore 21201, USA.

Find articles by Margaretten, K. in:JCI |PubMed |Google Scholar

Division of Pediatric Gastroenterology and Nutrition, University of Maryland School of Medicine, Baltimore 21201, USA.

Find articles by Ding, X. in:JCI |PubMed |Google Scholar

Division of Pediatric Gastroenterology and Nutrition, University of Maryland School of Medicine, Baltimore 21201, USA.

Find articles by Guandalini, S. in:JCI |PubMed |Google Scholar

Division of Pediatric Gastroenterology and Nutrition, University of Maryland School of Medicine, Baltimore 21201, USA.

Find articles by Comstock, L. in:JCI |PubMed |Google Scholar

Division of Pediatric Gastroenterology and Nutrition, University of Maryland School of Medicine, Baltimore 21201, USA.

Find articles by Goldblum, S. in:[JCI](/search/results?q=author.first%5Fname%3A%22S E%22+author.last%5Fname%3A%22Goldblum%22&search%5Ftype=advanced) |PubMed |Google Scholar

Published August 1, 1995 -More info

Published August 1, 1995 -Version history

View PDF

Abstract

The intracellular signaling involved in the mechanism of action of zonula occludens toxin (ZOT) was studied using several in vitro and ex vivo models. ZOT showed a selective effect among various cell lines tested, suggesting that it may interact with a specific receptor, whose surface expression on various cells differs. When tested in IEC6 cell monolayers, ZOT-containing supernatants induced a redistribution of the F-actin cytoskeleton. Similar results were obtained with rabbit ileal mucosa, where the reorganization of F-actin paralleled the increase in tissue permeability. In endothelial cells, the cytoskeletal rearrangement involved a decrease of the soluble G-actin pool (-27%) and a reciprocal increase in the filamentous F-actin pool (+22%). This actin polymerization was time- and dose-dependent, and was reversible. Pretreatment with a specific protein kinase C inhibitor, CGP41251, completely abolished the ZOT effects on both tissue permeability and actin polymerization. In IEC6 cells ZOT induced a peak increment of the PKC-alpha isoform after 3 min incubation. Taken together, these results suggest that ZOT activates a complex intracellular cascade of events that regulate tight junction permeability, probably mimicking the effect of physiologic modulator(s) of epithelial barrier function.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history