The tight Junction (TJ) represents the structural basis for the permeability barrier found in the kidney and other epithelial tissues. It is a macromolecular complex composed of both transmembrane and cytosolic proteins which also interacts with the cytoskeleton. Derangement sin TJ function are thought to occur in several pathophysiological states inclusive of hepatitis, CROHN~s disease and a variety of toxic and inflammatory disorders affecting the kidney. Recovery from these insults is associated with normalization of TJ function. Understanding the factors governing TJ assembly and function are therefore likely to have a significant impact on our approach to therapy, particularly if measures to stabilize the complex are subsequently forthcoming. However, to date, information pertaining to the formation of a functional TJ complex is limited, and no credible model for TJ bioassembly has been presented. In this proposed series of experiments, we intended to characterize the synthesis, folding and intracellular transport of proteins involved in TJ assembly and thereby, evaluate our proposed series model for this process. The degree of cell-cell contact likely plays a critical role and we anticipate the this process will require the synchronized interactions of proteins transiting the secretory pathway with those that are cytosolically assembled.
| George, Sathish K; Meyer, Tobias N; Abdeen, Omaran et al. (2004) Tunicamycin preserves intercellular junctions, cytoarchitecture, and cell-substratum interactions in ATP-depleted epithelial cells. Biochem Biophys Res Commun 322:223-31 |
