Composition of major intercellular junctions in the polarized intestinal epithelium. Schematic presentation of specific junctional complexes and associated signaling pathways. (A) Tight junctions (TJs) contain at least four major groups of transmembrane proteins: the JAMs, claudins, occludin and a number of cytoplasmic peripheral proteins. While the transmembrane proteins mediate cell-to-cell adhesion, the cytosolic TJ complex connects to different factors (e.g. ZO-1/-2/-3, MUPP1 or cingulin) that link the involved transmembrane proteins to the actin-cytoskeleton. The integrity of TJs is maintained by a regulatory complex including atypical PKC (aPKC), Rac1, Cdc42, Par6 and Par3. (B) The calcium-dependent integrity of adherens junctions (AJs) is stabilized by binding of E-cadherin to the intracellular catenins. The carboxy-terminal domain of E-cadherin binds to the cytoplasmic protein β-catenin. p120-catenin binds to the juxtamembrane part of E-cadherin and stabilizes the AJ complex. The E-cadherin-β-catenin structure is connected to the actin-cytoskeleton via binding to α-catenin and Eplin. When the E-cadherin complex is disrupted, β-catenin can translocate into the nucleus and activate Tcf/LEF transcription factors. (C) Focal adhesions (FAs) are structural complexes that link the extracellular matrix (ECM) to the intracellular actin-cytoskeleton. They contain various integrin heterodimers which are transmembrane receptors composed of α and β chains. The extracellular integrin tail directly binds to ECM proteins such as fibronectin, while the cytoplasmic domain is linked to the actin-cytoskeleton via a large number of indicated adapter/signaling proteins to transmit signaling. (D) Hemidesmosomes are also located at the basal side of epithelial cells where they link laminins to the intracellular intermediate filament network. Thus, hemidesmosomes provide stable adhesion of epithelial cell layers to the basement tissue. They consist of integrin α6β4, CD151 and BP180 which are transmembrane proteins, while plectin and BPAG1e are located in the cytoplasm. Plectin mediates linkage of hemidesmosomes to the cytokeratin network and not to F-actin filaments.