Tight junctions and the molecular basis for regulation of paracellular permeability.
Tight junctions create a regulated paracellular barrier to the movement of water, solutes, and immune cells between both epithelial and endothelial cells. Recent progress has been made in identifying the proteins that create this barrier. The transmembrane protein occludin is an excellent candidate for the sealing protein and is bound on the cytoplasmic membrane surface to the proteins ZO-1 and ZO-2. Functions for ZO-1 and ZO-2 are suggested by their invertebrate homologues, one of which is a tumor suppressor and another is required in epidermal growth factor receptor signaling. Multiple cellular signaling pathways affect assembly and sealing of junctions. Dynamic regulation of perijunctional actin has emerged as a unifying hypothesis for controlling paracellular permeability. Understanding and manipulating permeability will require a more detailed molecular characterization of tight junction proteins and in particular a characterization of how cell signaling regulates their attachment to the perijunctional cytoskeleton.
D000199:Actins / Q000502:physiology; D000818:Animals; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D062793:Occludin; D010539:Permeability; D010750:Phosphoproteins / Q000502:physiology; D019108:Tight Junctions / Q000502:physiology*; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein
D000199:Actins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569046:TJP2 protein, human; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein