FIGURE 2:

New tricellular junction formation and functional importance of tricellular junctions. (A) Nascent tTJ formation after cytokinesis. When the cleavage furrow ingresses and the bicellular cell–cell junctions (green) from each side of the furrow meet, a new cell–cell interface between neighboring cells and two new vertices are formed. Angulin-1 (cyan) and then tricellulin are recruited to the newly formed vertices and build mature tTJs (blue). Formation of one tTJ is soon followed by the other. After cytokinesis, new tTJs either separate as the bicellular junctions between them elongate (top) or fuse and reorganize to make tTJs among a different combination of the cells (bottom). (B) tTJ formation during turnover of epidermal cells. TJs exist only at the second layer of stratum granulosum (SG2). The red dotted line in the top, en face view indicates the position of the cross-section view (bottom). The TJ-bearing cells at SG2 turn over sporadically. When a cell at SG2 is going lose its apical cell–cell junctions, new cell–cell junctions are formed at the basal side of the cell. These new cell–cell junctions are formed among three cells, including a neighboring cell in the SG2 layer and an underlying cell in the SG3 layer, and the new junctions are enriched with tTJ components such as angulin-1 and tricellulin. As the upper cell–cell junctions disappear, tTJ components of the new, lower cell–cell junctions gradually become focused at cell vertices. (C) Cell intercalation during convergent extension. In type I/II/III transition, shortening of cell–cell junctions perpendicular to the tissue elongation axis results in fusion of two tricellular junctions and formation of a four-way junction. Then the four-way junction becomes two tricellular junctions along the elongation axis. In some cases, instead of four-way junctions, more than four cells make a multiway junction (also called a rosette; not depicted here). (D) tTJs (blue) are important for barrier function of the sensory epithelium and viability of hair cells in the inner ear. OHC, outer hair cells. (E) Tricellular junctions are involved in pathogenesis of versatile species of bacteria. S. flexneri spreads to neighboring cells via the tricellular junctions by utilizing host actin and penetrating through the corners of infected cells. C. difficile secretes the binary toxin CDT, which binds to angulin-1, a tTJ component. CDT is then incorporated into the cell by endocytosis and modulates actin and microtubules, which induces cell protrusions at the cell surface and contributes to adherence and colonization of the bacteria. Group A Streptococcus and enteropathogenic E. coli preferentially bind to tricellular junctions and invade into submucosal tissues through tricellular junctions.