Differential pathways of claudin oligomerization and integration into tight junctions

Tight junctions are the critical intercellular structure required to establish an epithelial barrier. Among the several classes of proteins required to form tight junctions are the tetraspan transmembrane proteins known as claudins that directly determine paracellular permeability. Considerable progress has been made in understanding how incorporation of different claudins into tight junctions increase or decrease paracellular permeability and ion selectivity. However, it has proven difficult to identify discrete steps in claudin assembly and whether claudins exist in distinct oligomerization states prior to tight junction assembly. Studies of homomeric and heteromeric claudin-claudin interactions using complementary techniques suggest a diversity of pathways used by different claudins to oligomerize and integrate into tight junctions.