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Tight junctions (zonulae occludens) are critical to the maintenance of cell polarity and intercellular barriers between epithelial and endothelial cells. Among the barriers formed by the tight junctions is the critical blood-brain barrier. Protein components of the tight junctions include actin filaments, symplekin, occludin, Rab3B, AF-6, 7H6, ZO-1 and ZO-2. The human occludin protein is 522 amino acids with four transmembrane domains in the first half of the protein. Two glycine/tyrosine-rich extracellular loops are involved in cell-cell interactions. In the cytoplasm, occludin interacts with ZO-1 through its intracellular C-terminus. A possible function of ZO-1 may be to link the adherens components, like occludin, to the submembraneous actin cytoskeleton. Experimental breakdown of the tight junctions at the blood-brain barrier results in redistribution of vinculin and loss of ZO-1 and Occludin. Taken together, these data indicate that occludin and ZO-1 are critical elements in the formation of tight junctions and may also serve an important role in signaling and tumor suppression.
