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Research Article Free access | 10.1172/JCI118114

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

A Fasano, 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.

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

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

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

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

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

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

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

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

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

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Published August 1, 1995 - More info

Published in Volume 96, Issue 2 on August 1, 1995
J Clin Invest. 1995;96(2):710–720. https://doi.org/10.1172/JCI118114.
© 1995 The American Society for Clinical Investigation
Published August 1, 1995 - Version history
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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.

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