Biochemical components of tight junction: transmembrane protein: claudin, occludin, junctional adhesion molecule (JAM) seal the paracellular space between adjacent epithelial cells, separating the cell into apical compartment and basolateral compartment. Claudin constitutes the paracellular barrier and pore by homogenic and heterogenic interaction. C-termini of claudin, occludin, and JAM have PDZ binding domain linking to scaffold ZO protein. ZO protein can bind directly [60] to cytoskeleton actin filament. Protein kinase, protein phosphatase, and transcription factors (not shown in the figure) can interact with cytosolic part of claudin, occludin and JAM and ZO protein to regulate tight junction assembly

Molecular model of paracellin-1/claudin-16. Claudin-16 has four predicted transmembrane domains with intracellular N- and C-termini. Acidic residues in the first extracellular domain that participate in cation permeation (as evidenced by neutralizing mutations that preserve normal expression and trafficking but reduce paracellular Na permeability [17]), probably by affecting pore electronegativity [20], are shaded red; those that do not appear to be important for permeation are shaded yellow. FHHNC mutations that preserve paracellin-1 expression and trafficking but impair permeability are shaded blue [17]; those that abolish expression or cause miss-trafficking are mostly uninformative of paracellin-1 function and are not shown. Serine-217 (purple) is phosphorylated by PKA and thereby facilitates trafficking to the tight junction [45]. Cysteines located at the intracellular end of the second and fourth transmembrane domains and shaded brown are homologous to those that are palmitoylated and participate in tight junction trafficking in other claudins [61]. A C-terminal PDZ-binding motif (TRV) that is required for binding to ZO1 and tight junction trafficking is shaded green [62]