Connexin 43 (Cx43) is a gap junction (GJ) protein widely expressed in mammalian tissues that mediates cell-to-cell coupling. Intercellular channels comprising GJ aggregates form from docking of paired connexons, with one each contributed by apposing cells. Zonula occludens-1 (ZO-1) binds the carboxy terminus of Cx43, and we have previously shown that inhibition of the Cx43/ZO-1 interaction incr...

The gastrointestinal epithelial layer forms a physical and biochemical barrier that maintains the segregation between host and intestinal microbiota. The integrity of this barrier is critical in maintaining homeostasis in the body and its dysfunction is linked to a variety of illnesses, especially inflammatory bowel disease. Gut microbes, and particularly probiotic bacteria, modulate the barrie...

After the simulation of anoxia by ATP depletion of MDCK cell monolayers with metabolic inhibitors, the tight junction (TJ) is known to become structurally perturbed, leading to loss of the permeability barrier. Peripheral TJ proteins such as zonula occludens 1 (ZO-1), ZO-2, and cingulin become extremely insoluble and associate into large macromolecular complexes (T. Tsukamoto and S. K. Nigam. J...

The tight junction is the most apical intercellular junction of epithelial cells and regulates transepithelial permeability through the paracellular pathway. To examine possible functions for the tight junction-associated protein ZO-1, C-terminally truncated mutants and a deletion mutant of ZO-1 were epitope tagged and stably expressed in corneal epithelial cell lines. Only full-length ZO-1 and...

ZO-1 is a 210- to 220-kDa peripheral membrane protein associated with the cytoplasmic surface of the epithelial tight junction. Because ZO-1 may interact with other unidentified tight junction proteins, we have looked for other polypeptides that bind to ZO-1. A 160-kDa polypeptide was identified that coimmunoprecipitates with ZO-1 from detergent extracts of metabolically labeled Madin-Darby can...

BACKGROUND Several factors favour the development of kidney lesions. We examined the role of oxidative stress in the onset of renal alterations that occur in Zucker obese (ZO) fa/fa rats. METHODS Kidney structure, biological data, glycation parameters, advanced glycation end products (AGE), thiobarbituric acid-reactive substances (TBARS), circulating antibodies anti-malondialdehyde (MDA)-modi...

We tested the hypothesis that increased production of nitric oxide (NO*) by inducible NO* synthase (iNOS) is a key factor responsible for alterations in the expression, localization, and function of key tight junction (TJ) proteins in mice challenged with lipopolysaccharide (LPS, endotoxin). Endotoxemia was associated with hepatobiliary epithelial barrier dysfunction, as evidenced by increased ...

Cingulin, a protein component of the submembrane plaque of tight junctions (TJ), contains globular and coiled-coil domains and interacts in vitro with several TJ and cytoskeletal proteins, including the PDZ protein ZO-1. Overexpression of Xenopus cingulin in transfected Xenopus A6 cells resulted in the disruption of endogenous ZO-1 localization, suggesting that cingulin functionally interacts w...

The structure and function of both adherens (AJ) and tight (TJ) junctions are dependent on the cortical actin cytoskeleton. The zonula occludens (ZO)-1 and -2 proteins have context-dependent interactions with both junction types and bind directly to F-actin and other cytoskeletal proteins, suggesting ZO-1 and -2 might regulate cytoskeletal activity at cell junctions. To address this hypothesis,...