Tight junction regulation in celiac disease: role of larazotide acetate

Epithelial layers are integral for many physiological processes and are maintained by intercellular adhesive structures. During disease, these structures can disassemble, leading to breakdown of epithelia. TJs (tight junctions) are one type of intercellular adhesion. Loss of TJs has been linked to the pathogenesis of many diseases. The present review focuses on the role of vesicle trafficking in regulation of TJs, in particular trafficking of the TJ protein occludin. We examine how endocytosis and endosomal recycling modulate occludin localization under steady-state conditions and during stimulated TJ disassembly.

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Role of flavonoids in intestinal tight junction regulation

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2010.08.001 ◽

2011 ◽

Vol 22 (5) ◽

pp. 401-408 ◽

Cited By ~ 122

Author(s):

Takuya Suzuki ◽

Hiroshi Hara

Keyword(s):

Tight Junction ◽

Tight Junction Regulation

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Protein kinase Cζ phosphorylates occludin and promotes assembly of epithelial tight junctions

Biochemical Journal ◽

10.1042/bj20110587 ◽

2011 ◽

Vol 437 (2) ◽

pp. 289-299 ◽

Cited By ~ 54

Author(s):

Suneet Jain ◽

Takuya Suzuki ◽

Ankur Seth ◽

Geetha Samak ◽

Radhakrishna Rao

Keyword(s):

Protein Kinase ◽

Tight Junction ◽

Tight Junctions ◽

Intercellular Junctions ◽

Cell Monolayers ◽

Terminal Domain ◽

Tight Junction Regulation ◽

Epithelial Tight Junctions ◽

Zona Occludens

Protein kinases play an important role in the regulation of epithelial tight junctions. In the present study, we investigated the role of PKCζ (protein kinase Cζ) in tight junction regulation in Caco-2 and MDCK (Madin–Darby canine kidney) cell monolayers. Inhibition of PKCζ by a specific PKCζ pseudosubstrate peptide results in redistribution of occludin and ZO-1 (zona occludens 1) from the intercellular junctions and disruption of barrier function without affecting cell viability. Reduced expression of PKCζ by antisense oligonucleotide or shRNA (short hairpin RNA) also results in compromised tight junction integrity. Inhibition or knockdown of PKCζ delays calcium-induced assembly of tight junctions. Tight junction disruption by PKCζ pseudosubstrate is associated with the dephosphorylation of occludin and ZO-1 on serine and threonine residues. PKCζ directly binds to the C-terminal domain of occludin and phosphorylates it on threonine residues. Thr403, Thr404, Thr424 and Thr438 in the occludin C-terminal domain are the predominant sites of PKCζ-dependent phosphorylation. A T424A or T438A mutation in full-length occludin delays its assembly into the tight junctions. Inhibition of PKCζ also induces redistribution of occludin and ZO-1 from the tight junctions and dissociates these proteins from the detergent-insoluble fractions in mouse ileum. The present study demonstrates that PKCζ phosphorylates occludin on specific threonine residues and promotes assembly of epithelial tight junctions.

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