Temperature-sensitive cortical condensation modulates mechano-response at Tricellular Junctions

A general mechanism to maintain epithelial integrity during cell movements is to couple adhesion strength with mechanical force. Mechanosensitive proteins are recruited to adhesion sites to reinforce cell-cell or cell-matrix linkage in response to elevated tension. However, subcellular mechanisms for highly dynamic protein transport into and out of tension-bearing structures remain elusive. Furthermore, it is still unknown whether mechanosensitivity can be modulated by physiological signals in vivo. Here we revealed a direct "edge-to-vertex" route of Canoe/Afadin transport to tricellular junctions under tension, which relies on an obligatory binding partner Mbt/PAK. Without Mbt/PAK, Canoe/Afadin becomes insensitive to cytoskeletal tension and forms "tactoid-shaped" condensates directly at bicellular junctions. Remarkably, a temporary increase in temperature within the physiological range dissolves these condensates, allowing Canoe/Afadin to regain mechanosensitivity and enrichment at tricellular junctions. Functionally, the localization of Mbt/PAK at cell junctions oscillates during synchronous cell division within embryonic mitotic domains, enabling dynamic adjustments of Canoe/Afadin mechanosensitivity to preserve epithelial integrity in rapidly dividing tissues. Collectively, our findings suggest a physiological process in which the state of protein condensation, regulated by biochemical inputs, can supersede mechanical signals to modulate adhesion strength during cell division.