Claudin switching: Physiological plasticity of the Tight Junction

• The paracellular barrier is provided by Tight Junctions.
• Tight Junction barrier properties are determined by claudin expression.
• There are multiple claudins within the Tight Junction.
• Claudins are exchanged during intestinal tissue homeostasis.
• The Tight Junction is a highly adaptive, dynamic structure.

Tight Junctions (TJs) are multi-molecular complexes in epithelial tissues that regulate paracellular permeability. Within the TJ complex, claudins proteins span the paracellular space to form a seal between adjacent cells. This seal allows regulated passage of ions, fluids, and solutes, contingent upon the complement of claudins expressed. With as many as 27 claudins in the human genome, the TJ seal is complex indeed. This review focuses on changes in claudin expression within the epithelial cells of the gastrointestinal tract, where claudin differentiation results in several physiologically distinct TJs within the lifetime of the cell. We also review mechanistic studies revealing that TJs are highly dynamic, with the potential to undergo molecular remodeling while structurally intact. Therefore, physiologic Tight Junction plasticity involves both the adaptability of claudin expression and gene specific retention in the TJ; a process we term claudin switching.