Actin, Claudin-16, MUPP1, WNK4, Cingulin, Claudin-5, JAM2, LYRIC, CSDA, ZO-1, ZO-3, Claudin 1, Claudin 19, JAM3, AF-6, ITGB1, Claudin 3, Claudin 2, Claudin 4, Claudin-8, CDX1, Tcf(Lef), Myosin II, ZO-2, CDX2, Occludin, SP1, Occludin, Caveolin-1, Prr1, SNAIL1, Claudin 7, Claudin 3, Claudin-5, TITF1, Claudin-18, Claudin 1, Claudin-14, Claudin 2, JAM1, Claudin-11, Claudin-14
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 .
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 .
Actin filament-binding protein AF-6 serves as a linker of the Actin cytoskeleton to the plasma membrane at the TJ sites .
Cingulin is a functionally important component of TJ. It links the submembrane plaque domain of TJ to the actomyosin cytoskeleton .
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 .
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 .
Interactions between Nectin ( Prr1 ), AF-6 and Occludin suggest a role of the nectin-afadin system in the organization of TJs in epithelial cells .
WNK lysine deficient protein kinase 4 ( WNK4 ) phosphorylates Claudins 1-4 involved in the regulation of paracellular ion permeability .
ZO-1 -associated Y-box factor ZONAB ( CSDA ) regulates epithelial cell proliferation and cell density .
Transcription factors Tcf(Lef), TITF1, CDX1, CDX2 and SNAIL1 are involved in the transcriptional regulation of expression of the genes encoding TJ proteins .