Multicellular organisms are separated from external environment by a layer of epithelial cells whose integrity is maintained by intercellular junction complexes composed of tight junctions (TJ), adherens junctions, and desmosomes. Tight cell junctions serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets.

A group of integral membrane proteins, Occludin, Claudins, and Junction adhesion molecules (JAM 1, JAM 2 and JAM3), interact with an increasingly complex array of tight junction plaque proteins to regulate paracellular solute and water flux and integrate other diverse cell functions [1].

TJ plaque proteins, such as Zonula occludens ZO-1, ZO-2 and ZO-3, serve as links between the integral TJ proteins and the Actin cytoskeleton and as adapters for the recruitment of cytosolic molecules implicated in cell signaling [2].

Actin filament-binding protein AF-6 serves as a linker of the Actin cytoskeleton to the plasma membrane at the TJ sites [3].

Cingulin is a functionally important component of TJ. It links the submembrane plaque domain of TJ to the actomyosin cytoskeleton [4].

Multi-PDZ domain protein 1 (MUPP1) accumulates at the TJ in epithelial cells through its binding to Claudins and JAMs. MUPP1 is believed to function as a multivalent scaffold protein that recruits various proteins to TJ [5].

Metadherin (LYRIC) colocalizes with ZO-1 and Occludin in polarized epithelial cells. This protein is most likely not involved in the TJ formation as a structural component. However, it is required for the maturation of the TJ complex [6].

Interactions between Nectin (Prr1), AF-6 and Occludin suggest a role of the nectin-afadin system in the organization of TJs in epithelial cells [7].

WNK lysine deficient protein kinase 4 (WNK4) phosphorylates Claudins 1-4 involved in the regulation of paracellular ion permeability [8].

ZO-1-associated Y-box factor ZONAB (CSDA) regulates epithelial cell proliferation and cell density [9].

Transcription factors Tcf(Lef), TITF1, CDX1, CDX2 and SNAIL1 are involved in the transcriptional regulation of expression of the genes encoding TJ proteins [1].

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