Diffusion of solutes is prevented across certain barriers by the formation of tight junction seals. Occludin and Cingulin interact with other proteins to direct the formation and regulation of tight junctions. Cingulin, a protein component of the submembrane plaque of tight junctions (TJ), contains globular and coiled-coil domains and interacts in vitro with several TJ and cytoskeletal proteins, including the PDZ protein ZO-1. Cingulin binding has also been shown to inhibit RhoA activation and signaling with increased Cingulin expression in confluent cells, causing downregulation of RhoA by inhibiting GEF-H1/Lfc.