Date of Award


Document Type

Thesis campus only




Epithelial cells are localized throughout the body and play a significant role in the physiology of an organism. They line surfaces and are able to form a selectively permeable barrier to the bloodstream. They do this via the tight junction, which localizes to the apical region of the cell. The tight junction is selectively permeable to both the size and charge of solutes and is dependent on the composition of proteins within the tight junction. Some important tight junction proteins of note are claudins, occludens, and zonula occludens. We have focused our studies on the role of zonula occludens-1 and how its C-terminal ZU5 domain interacts with other aspects of the tight junction and the role it plays in the function of the tight junction. To do this, we characterize the interactions between ZU5 and F-actin as well as ZU5 and the rho-GTPase ARHGEF11, and determine how the ZU5 domain affects the permeability of the tight junction. We hypothesize that ZU5 is interacting with F-actin within the cytoskeleton and helps to stabilize that interaction as well as the junction as a whole. We show here that ZU5 helps anchor zonula occludens-1 to the tight junction, and helps to stabilize the tight junction as a whole. We have determined that ZU5 is important for maintaining the selective permeability of epithelial cells. We suggest that the interactions between the ZU5 domain and F-actin are due to the hydrophobic pocket located within the ZU5 domain.