CK2-mediated phosphorylation of occludin residue S408 regulated tight junction structure, dynamic behavior, and barrier function. (A) CK2-mediated phosphorylation of S408 enhances occludin self-association, increases the occludin mobile fraction, and reduces occludin association with ZO-1, claudin-1, and claudin-2. This promotes flux across claudin-2 pores, thereby increasing paracellular cation flux. (B) When dephosphorylated at S408, occludin is stabilized at the TJ through enhanced association with ZO-1 via the U5-GuK domain. ZO-1 also facilitates indirect interactions between occludin and claudin-2, which associates with ZO-1 via the PDZ1 domain, thereby acting as a scaffold to organize a complex. As a result, dynamic behaviors of occludin, ZO-1, and claudin-2 converge, and function of claudin-2 paracellular pores is reduced. From Raleigh et al. 2011. J Cell Biol.