The Dual Role of Zonula Occludens (ZO) Proteins

Bauer, Hannelore; Zweimueller-Mayer, Josef; Steinbacher, Peter; Lametschwandtner, Alois; Bauer, Hans-Christian

doi:10.1155/2010/402593

Cited by 190 publications

(160 citation statements)

References 106 publications

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“…Significantly, CDH1 and TJP1 proteins had a more punctate distribution. In the case of TJP1, the protein was often localized in the nucleus, suggesting that inhibition of GRHL function interferes with the shuttling of TJP1 between the nucleus and cell membrane (21).…”

Section: Grhl2 Regulates the Expression Of Multiple Genes In Undiffermentioning

confidence: 99%

Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium

Gao

Vockley

Pauli

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Most of the airways of the human lung are lined by an epithelium made up of ciliated and secretory luminal cells and undifferentiated basal progenitor cells. The integrity of this epithelium and its ability to act as a selective barrier are critical for normal lung function. In other epithelia, there is evidence that transcription factors of the evolutionarily conserved grainyheadlike (GRHL) family play key roles in coordinating multiple cellular processes required for epithelial morphogenesis, differentiation, remodeling, and repair. However, only a few target genes have been identified, and little is known about GRHL function in the adult lung. Here we focus on the role of GRHL2 in primary human bronchial epithelial cells, both as undifferentiated progenitors and as they differentiate in air–liquid interface culture into an organized mucociliary epithelium with transepithelial resistance. Using a dominant-negative protein or shRNA to inhibit GRHL2, we follow changes in epithelial phenotype and gene transcription using RNA sequencing or microarray analysis. We identify several hundreds of genes that are directly or indirectly regulated by GRHL2 in both undifferentiated cells and air–liquid interface cultures. Using ChIP sequencing to map sites of GRHL2 binding in the basal cells, we identify 7,687 potential primary targets and confirm that GRHL2 binding is strongly enriched near GRHL2-regulated genes. Taken together, the results support the hypothesis that GRHL2 plays a key role in regulating many physiological functions of human airway epithelium, including those involving cell morphogenesis, adhesion, and motility.

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Section: Grhl2 Regulates the Expression Of Multiple Genes In Undiffermentioning

confidence: 99%

Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium

Gao

Vockley

Pauli

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…ZO-1 is one of three zonula occludens proteins belonging to a family of multi-domain proteins known as the membrane-associated guanylate kinase homologs (MAGUKs) (Fanning et al 1998). Previous studies have shown MAGUKs are not only essential structural proteins at the site of tight and gap junctions but also function in signal transduction pathways related to gene expression and cell behavior (Bauer et al 2010). ZO-1 is found in acinar and ductal cells of salivary epithelium (Maria et al 2008) and is critical for claudin polymerization (Umeda We were able to demonstrate that ZO-1 protein expression levels are unaltered in NOD/ShiLtJ mice as compared with control mice (Fig.…”

Section: Discussionmentioning

confidence: 99%

Zonula Occludens-1, Occludin and E-cadherin Expression and Organization in Salivary Glands with Sjögren’s Syndrome

Mellas

Leigh

Nelson

et al. 2014

J Histochem Cytochem.

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Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder that causes secretory dysfunction of the salivary glands leading to dry mouth. Previous studies reported that tight junction (TJ) proteins are down-regulated and lose polarity in human minor salivary glands with SS, suggesting that TJ structure is compromised in SS patients. In this paper, we utilized the NOD/ShiLtJ mouse with the main goal of evaluating this model for future TJ research. We found that the organization of apical proteins in areas proximal and distal to lymphocytic infiltration remained intact in mouse and human salivary glands with SS. These areas looked comparable to control glands (i.e., with no lymphocytic infiltration). TJ staining was absent in areas of lymphocytic infiltration coinciding with the loss of salivary epithelium. Gene expression studies show that most TJs are not significantly altered in 20-week-old NOD/ShiLtJ mice as compared with age-matched C57BL/6 controls. Protein expression studies revealed that the TJ proteins, zonula occludens-1 (ZO-1), occludin, claudin-12, as well as E-cadherin, do not significantly change in NOD/ShiLtJ mice. Our results suggest that ZO-1, occludin and E-cadherin are not altered in areas without lymphocytic infiltration. However, future studies will be necessary to test the functional aspect of these results.

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“…Perhaps the most well-known tight junction proteins are the Zonula Occludens (ZO) proteins, which act as scaffolding in the plasma membrane and provide a cytoplasmic structural anchor for the paracellular protein complexes [3]. Tight junctions also serve as a primary barrier or channel through which solutes and ions are selectively transported through the intercellular space.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Lignite Extract Supplement on Intestinal Barrier Function in Glyphosate-Mediated Tight Junction Injury

Gildea¹,

Roberts²,

Bush³

2017

J Clin Nutr Diet

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The Dual Role of Zonula Occludens (ZO) Proteins

Cited by 190 publications

References 106 publications

Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium

Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium

Zonula Occludens-1, Occludin and E-cadherin Expression and Organization in Salivary Glands with Sjögren’s Syndrome

Protective Effects of Lignite Extract Supplement on Intestinal Barrier Function in Glyphosate-Mediated Tight Junction Injury

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