Cell adhesion Tight junctions
Tight junctions Multicellular organisms are separated from external environment by a layer ofepithelial cells whose integrity is maintained by intercellular junction complexescomposed of tight junctions (TJ), adherens junctions, and desmosomes. Tight celljunctions serve as a physical barrier to prevent solutes and water from passing freelythrough the paracellular space between epithelial or endothelial cell sheets. A group of integral membrane proteins, Occludin, Claudins, andJunction adhesion molecules ( JAM 1, JAM 2 and JAM3 ), interact with anincreasingly complex array of tight junction plaque proteins to regulate paracellularsolute 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 andas adapters for the recruitment of cytosolic molecules implicated in cell signaling. Actin filament-binding protein AF-6 serves as a linker of the Actincytoskeleton to the plasma membrane at the TJ sites . Cingulin is a functionally important component of TJ. It links the submembraneplaque domain of TJ to the actomyosin cytoskeleton . Multi-PDZ domain protein 1 ( MUPP1 ) accumulates at the TJ in epithelial cellsthrough its binding to Claudins and JAMs. MUPP1 is believed to function asa multivalent scaffold protein that recruits various proteins to TJ . Metadherin ( LYRIC ) colocalizes with ZO-1 and Occludin inpolarized epithelial cells. This protein is most likely not involved in the TJformation as a structural component. However, it is required for the maturation of the TJcomplex . Interactions between Nectin ( Prr1 ), AF-6 and Occludin suggest arole of the nectin-afadin system in the organization of TJs in epithelial cells . WNK lysine deficient protein kinase 4 ( WNK4 ) phosphorylates Claudins1-4 involved in the regulation of paracellular ion permeability . ZO-1 -associated Y-box factor ZONAB ( CSDA ) regulates epithelial cellproliferation and cell density . Transcription factors Tcf(Lef), TITF1, CDX1, CDX2 andSNAIL1 are involved in the transcriptional regulation of expression of the genesencoding TJ proteins .