Epithelial cells in the epithelial cellular sheet are often represented as polygons. In a macroscopic view, tight junctions (TJs) circumscribe each cell as a belt, such that the intercellular spaces within the cellular sheet are continuously sealed. However, TJs cannot practically seal some exceptional regions, namely tricellular contacts, where the corners of three polygonal epithelial cells meet. There are three plasma membranes at tricellular contacts, while TJs are zipper-like structures formed between two plasma membranes. How is the extracellular space at tricellular contacts plugged? Tricellular contacts have specialized structures of TJs, termed tricellular tight junctions (tTJs), which extend from apical to basal direction at the center of tricellular contacts to form very narrow tubes as diffusion barriers. We identified angulin family proteins, including angulin-1/LSR, angulin-2/ILDR1 and angulin-3/ILDR2, as molecular components of tTJs. We demonstrated that angulins are required for full barrier function of the epithelial sheet and recruit tricellulin, another tTJ-associated membrane protein, to tTJs. However, detailed mechanism of tTJ formation and functional difference of angulins in the epithelial barrier function remain elusive. Moreover, the structure, behavior and physiological function of tricellular contacts still remain elusive despite their potential significance in epithelial biology. We address these issues by analyzing the function of the angulin-tricellulin system by cell biological and physiological approaches.

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