"Barrierology" : Tight Junctions and Human Diseases

Tight junctions are intercellular junctions adjacent to the lateral end of the apical membrane. They have two functions: the barrier （or gate） function and the fence function. The barrier function of tight junctions regulates the passage of ions, water, and various macromolecules, even of cancer cells, through paracellular spaces. The barrier function is thus relevant to edema, jaundice, diarrhea and blood-borne metastasis. The blood-brain barrier exclusively depends on this function of tight junctions of endothelial cells. On the other hand, the fence function maintains cell polarity. In other words, tight junctions work as a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membranes. This function is deeply involved in cancer cell biology, in terms of loss of cell polarity. We have been trying to expand our understanding of molecular regulation of tight junctions to human diseases. In this review, we introduce three projects currently ongoing; studies on tight junctions of hepatocytes deeply related to jaundice, tight junctions of endothelial cells crucial for the blood-brain barrier, and the formation and regulation of tight junctions during establishment of cell polarity.departmental bulletin pape